Development Cooperation During The Recent Years Biology Essay

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Medicinal plants have acquired increasing significance in development cooperation during the recent years. Their value and conservation are cross-sectoral concerns that embrace not only health care but also nature conservation, biodiversity, economic assistance, trade and legal aspects (e.g. intellectual property). Even today the majority of the world's population is dependent upon folk medicine and thus on the use of plants and plant extracts. This is particularly true for poorer sections of the population in developing countries, because natural remedies were not only cheaper than modern medicines but are often the only medicine available in remote rural areas (according to the WHO 80 per cent of the world's population is dependent on health care provided by medicinal plants). Besides serving medical and cultural functions, medicinal plants in developing countries also had an important economic role. The gathering of wild medicinal herbs frequently provides income socially and economically to groups such as smallholders and landless shepherds. In addition, medicinal plants were easily integrated into traditional crops such as maize, beans and vegetables. The differing harvest times enable the farmers to distribute their income more equally over the entire year. Small-scale traders and industries also advantage from being able to buy dried medicinal plants and process them into teas, ointments and tinctures for the local market. But the commercial importance of medicinal plants extends far beyond the national markets in developing countries. Germany alone imports medicinal plants worth over 75 million euros per year. Most of the plants come from developing and transforming countries. The viable use of plant material can therefore considerably improve trade balances in the countries of origin and offers major potential in terms of development. The basis for this is the unique biodiversity that exists in the advancing countries, where 90 per cent of Earth's genetic diversity is to be found.1

Herbal medicine

All over the globe, herbs represent a comeback and herbal 'renaissance'. The herbal products today design safety in contrast to the synthetics that are regarded as unsafe to human and environment. Although herbs had been set for their flavouring, aromatic and medicinal qualities for centuries. For a while the manufactured products of the modern age beat out their importance. However, the blind dependence on manufactured products is over and people are returning to the naturals with hope of security and safety. Over three-quarters of the world population depends mainly on plants and plant extracts for health care. More than 30% of the entire plant species, at one time or other was used for medicinal purposes. It is estimated that world market for plant derived products may account for about Rs.2,00,000 crores. Presently, Indian contribution is less than Rs.2000 crores. Indian export of raw drugs has steadily grown at 26% to Rs.165 crores in 1994-'95 from Rs.130 crores during 1991-'92. The annual production of medicinal and aromatic plant's raw material is about Rs.200 crores. By the year 2000, this is likely to reach US $1150 and by 2050 US $5 trillion.

It has been computed that in developed countries such as United States, plant products constitute as much as 25% of the total drugs, while in fast developing countries such as India and China, the contribution is 80%. Thus, the industrial importance of medicinal plants is much more to countries such as India than to rest of the world. They provide two third of the plants used in the health care system and in modern system of medicine of rural population depend on traditional systems of medicine.2

Native Substance versus Pure Substance

The aspiration is to produce the active principles of all medicinal plants as far as possible as pure substances, which could then be investigated in the same way as clearly-definable chemical compounds. A new trend evolved where such native substances were looked for, designating those phytopharmaceuticals. As a result it became possible to demonstrate the mode of action of many of the medicinal plants, and there can be no doubt that this can bring major advances in phytotherapy. This new technique which allowed the subject to become open to scientific investigation. At the same time, the field of phytochemistry had greatly expanded. It proved possible to isolate a remarkable number of plant principles, and then to prove their chemical formulae. This in turn lent fresh impetus to herbal medicine, and was greatly helped by the fact that new way had become available for the manufacture of standardized herbal pharmaceuticals. The pharmaceutical industry made a major contribution in this field.

Yet there are reservations when it comes to the proposal that one can elucidate the mode of action of every medicinal plant by preparing and asses its active principles in pure form. There has been a tendency to disregard any medicinal plant that did not fit easily into the new design concept of phytopharmaceuticals, writing them off as being of doubtful use. In many such cases we simply have not yet found the correct method of determining the mode of field. Considerable scope remains for research in this area.

First attempts have already been made to develop a unique discipline of phyto-pharmacology. Its function is to develop methods of assessing the total complex of a plant's medicinal actions, shows adequate significance for such whole-plant actions. This would represent a great step forward. It calls for very different ways of thinking - moving away from seeking and isolating pure principles, learning instead to take medicinal plants for what they are: a complete product of nature, with innumerable individual constituents, active principles and other substances that may also make a useful contribution to the total medicinal action. It should then also become possible to assess the many herbal miracle drug and extracts which continue to be so popular with the public. Most of them are made from ten, twenty or even more different medicinal plants, and many are found on old apothecaries' formulations. Until now it has not been possible to get an objective assessment of these multi-herb mixtures, however many have been recommended on the basis of practical experience.3


Herbal medicines are cost-effective and less expensive.

Another merit of herbal medicine is that it can be bought without any prescription.

They are available `in `ever` health`store. 

Herbal medicine and remedies are more effective than allopathic medicine for many ailments. 

The chemical medicine prescribed by a pharmacist may have certain negative side effects. However, many of the herbal medicines and remedies does not have negative side effects and softer than allopathic medicine. 

Disadvantages of Herbal Medicine

Like all forms of alternative health care, herbal medicine also has some demerits. Here are some of them. 

Treatment with herbal medicine and supplements would take some time. You should possess immense patience. 

They contain various ingredients and you should be sure that your body agrees with the ingredients and it is not allergic. 

Herbal remedies and medicine for certain ailments may have negative side effects. These side effects may not be revealed immediately, but would take months or even years. In the initial stages, if the herbal medicine is not agreeing with you, it is wise to stop using it. 

Remember, the government did not regulate herbal medicine industry. Hence, there is no quality assurance for herbal products. 

There are very few good practitioners of herbal medicine and it would be wise to ensure that you consult a good practitioner for using herbal medicine.4

Allopathic system of medicine

Allopathic medicine refers to the practice of conventional medicine that uses pharmacologically active agents or physical interventions to treat or suppress symptoms or pathophysiologic processes of diseases or conditions. It was coined by Samuel Hahnemann (1755-1843), a homeopath, in 1810. Although "allopathic medicine" was rejected as a term by mainstream physicians, it was adopted by alternative medicine advocates to refer pejoratively to conventional medicine. Allopathic medicine often refers to "the broad category of medical practice that is sometimes called Western medicine, biomedicine, evidence-based medicine, or modern medicine"5

Public seems to be fed up with Modern System (Synthetic drugs) mainly due to-

Only symptomatic relief is produced.

'Completion of treatment' is never a reality, more so in chronic ailments.

Frustrating side effects.

High cost involved.

Alternate system of medicine

The ancient Greeks postulated that health claims a balance of vital humors, Asian cultures considered that health depends on the balance and flow of vital energies through the body.6 Alternative system is a term commonly used to include all the healing practice "that does not fall within the area of conventional medicine". It is defined as "a variety of therapeutic or preventive health care practices, such as homeopathy, naturopathy, chiropractic and herbal medicine that do not follow generally accepted medical methods and may not have a scientific explanation for their effectiveness". Complementary and alternative medicine is the term for medical products and practices that are not part of standard care. Standard care is what medical doctors, osteopathic doctors and allied health professionals such as registered nurses and physical therapists practice. Alternative medicine means treatments that you can use behalf of standard ones. 7

Ayurveda system of Medicine

Ayurvedic medicine, also called Ayurveda, actualised in India several thousand years ago. The term "Ayurveda" combines the Sanskrit words ayur (life) and veda (science or knowledge). Thus, Ayurveda means "the science of life."8. Ayurveda considers humans beings in their totality and in their relationship with its approach is that disease occurs due to imbalance in the equilibrium of three doshas, restoration of which eliminates the disease. Thus it aim is not only curing the disease but also enhancing the body vitality to combat the disease and strengthen the immune system so the disease is automatically cured or prevented. According to Ayurveda there were three basic constituents of the physiological system. They are called Doshas and are classified into Vata, Pitta and Kapha. These correspond primarily to elements of air, fire and water. They determine the life processes of growth and decay.

There are seven Dhatus or tissues in the body. These are: Rasa- body fluids, Rakta- blood, Mansa-muscular tissue, Meda- adipose tissue, Asthi- bone tissue, Majja- nerve tissue and bone marrow, and Shukra- generative tissue. There are also waste products (Malas). There are many malas in the body- stool, urine, sweat, nails, hair etc. Health depends on equilibrium of all dhatus, doshas and malas both in quantity and quality.9

Unani System of Medicine

The Unani System of Medicine originated in Greece and was developed by Arabs into an elaborate medical science based on the frame work of the teaching of Buqrat (Hippocrates) and Jalinoos (Galen). from that time Unani Medicine has been kown as Greco-Arab Medicine. The unani system is based on Hippocatic theory of four humours viz. blood, phlegm, yellow bile and black bile, and the four qualities of states of living human body like hot, cold, moist and dry. They are represented as earth, water, fire and air, the Greek ideas were put by Arabian physician as seven principles (Umoor-e-Tabbiya) and included, element (Arkan), temperament (Mizaj), humours (Akhlat), organs (Aaza), sprit (Arwah), faculties (Qowa) and functions (Afaal). In this system is it believed that, these principles are responsible for the body constitution and its health, as well as, diseased conditions.10

Homeopathic System of Medicine

It is the system of treatment based on demonstrable laws and principles, which are -

a) The Law of Similars - It is also known as the Law of Cure. This law proves that the selected remedy is able to produce a range of symptoms in a healthy person similar to that observed in the patient, thus leading to the principle of Similia Similibus Curentur i.e. let likes be treated by likes. A simple example, the effects of peeling an onion are very similar to the symptoms of acute cold. The remedy prepared from the red onion, Allium cepa, is used to treat the type of cold in which the symptoms resemble those we get from peeling onion. The principle has been validated by millions of Homoeopaths all over the world.

b) The Law of Single Remedy - This law conducts to choose and administer such a single remedy, which is most similar to the symptom complex of the sick person at a time.

c) The Law of Minimum Dose - The similar remedy selected for a sick should be prescribed in minimum dose, so that when administered there is no toxic effects on the body. It just acts as a triggering and catalytic agent to stimulate and strengthen the existing defense mechanism of the body. It does not need to be repeated frequently.11

Homeopathy is a nonpoisonous form of medicine that was developed approximately 200 years ago by Dr. Samuel Hahnemann. The word homeopathy is supposed from two words: homoios meaning similar and pathos meaning suffering. Homeopathy uses highly diluted pathogens or other potentially toxic substances as remedies. These remedies spark healing responses in a person's immune system or provoke other body responses to treat the root causes of illness.12

Siddha System of Medicine

The Siddha system of medicine belongs to the Dravidian culture which is of pre-vedic period. According to Indian history prior to Aryans migration, the Dravidian was the first inhabitant of India of whom the Tamilians were the most prominent. The languages of India were divided into two great classes, the northern with Sanskrit and the southern with Dravidian language. The Siddha was flourished in south and Ayurveda prevalent in the north.

The Siddha System is largely curative in nature. The origin of Siddha system of medicine is assigned to the great Siddha Ayastiyar. The term Siddha refers to saints and persons known as Siddhars who achieved fruit in medicine. The Siddhars were expert scientists in ancient times. Eighteen Siddhars are believed to have contributed towards the development of the medical system. An examination of the ancient literature reveals that the vedic Aryas owed allegiance to the cult of Shiva and the worship of linga which later on absorbed by and incorporated into the vedic culture. The Shiv cult is associated with its medical counterpart, the Siddha system of medicine. Siddha system is one of the oldest systems of medicine in India. Siddha literature is in Tamil and it is practiced largely in Tamil speaking part of India, Sri Lanka, Malaysia and Singapore where the Dravidian civilization was prominent.9

Yoga and Naturopathy

Yoga means "It's a means of compressing one's evolution into a single life or a few months or even a few hours of one's bodily existence". Yoga is not a science but also an art of healthy living physically, mentally, morally and spiritually. It's systematic growth from his animal level to the currency, from there to the divinity, ultimately.12

During past, Yoga was considered very exotic and secret, being a forte of the hermits and saints who practiced it to attain spiritual enlightenment. But things have changed dramatically in recent years, with Yoga coming to light and catching the whims of the West. Yoga has now become a household word and has attained popularity, especially as a system of health care.

Although there are many definitions of Yoga, but they all emphasize the same thing, i.e. Yoga being the union of individual spirit (Jivatman) with the universal spirit (Parmatman), which is achieved by the practitioner. After the cessation of thought process in the highest stage of Samadhi (meditation) - the state of enlightenment and divine bliss.13

1.1 CNS Stimulant

All stimulant drugs cause an increase in general behavioral activity. When taken short-term (one or two weeks), they cause states of euphoria, optimism, and general feelings of well-being. Initial feelings of anorexia are frequent, a quality that leads to their use/abuse in weight loss products. Insomnia is also frequent. These responses indicate that the part of the brain which controls these functions, the hypothalamus, is strongly affected by these drugs and that the dopamine transmitter system is primarily involved in many of these effects. Other effects are:

decreased feelings of depression

increased thoughts and associations

increased talkativeness

increased blood pressure



decreased fatigue

Tolerance to stimulants

Tolerance to the mood-elevating and appetite-suppressing effects develops after about two weeks of daily use. Little tolerance develops to the behavioral-arousal effect, which is what makes these drugs useful in the long-term treatment of narcolepsy.

Abuse of Stimulants

A person who is addicted to stimulants, or who has had a long period of continuous use, will experience withdrawal symptoms if the drug is stopped abruptly. Symptoms of withdrawal from amphetamines and cocaine are very similar, mainly feelings of depression, fatigue, apathy, and general sluggishness, the opposite of the effects seen under the influence of these drugs.14

Classification of CNS Stimulants




Caffine, Theophyllin, Theobromine


Amphetamine, Dextroamphetamine, Methamphetamine,



Atropine. Cocain



Leptazol, Nikethamide, Ethamivan, Doxapran, Picrotoxin






Mechanism of Action of Amphetamine

Amphetamine and dextroamphetamine stimulates the release of norepinephrine from central adrenergic receptors. At higher dose, they cause release of dopamine from the mesocorticolimbic system and the nigrostriatal dopamine systems. Amphetamine may also act as a direct agonist on central 5-HT receptors and inhibits monoamine oxidase (MAO). In the periphery, amphetamines release noradrenaline by acting on the adrenergic nerve terminals and alpha- and beta-receptors. Modulation of serotonergic pathways may contribute to the calming effect.16

1.2 Diabetes Mellitus

The prevalence of diabetes mellitus is growing tremendously worldwide and is reaching epidemic proportions. It is estimated that there are currently 285 million people with diabetes worldwide and this number will increase to 438 million by the year 2030. The major proportion of this increase will occur in developing countries of the world where the disorder predominantly affects younger adults in the economically productive age group. There is also consensus that the South Asia region will include three of the top ten countries in the world (India, Pakistan and Bangladesh) in terms of the estimated absolute numbers of people with diabetes17.


The pancreas is a soft, elongated digestive gland which is grey-pink and 'feather-like' in appearance. It is about 15 cm in length, lobular and weighs about 80 g. It is retroperitoneal and extends transversely across the posterior abdominal wall from the curve of the duodenum to the hilum of the spleen. The right side lies across the vertebral bodies of L1-L3. It is posterior to the stomach and the transverse mesocolon is attached to its anterior margin. It is located in the left hypochondriac and epigastric regions. The pancreas is both an endocrine and an exocrine gland.18

98% by weight is exocrine. Acinar cells: produce and secrete bicarbonate and digestive enzymes into the upper GI.

2% endocrine: Islets of Langerhans

Alpha cells:

Located mostly in the periphery of the dorsal pancreatic bud Secrete glucagons, proglucagon, Glucagon-like peptides (GPL 1 & 2).

Beta cells:

Located in the center of the Islets Secrete Insulin, C peptide, and Proinsulin.

Delta cells :

Dispersed Secrete somatostatin.

F cells:

Located in the periphery of the ventral pancreatic buds Secrete pancreatic polypeptide .

Blood Supply:

First to the center of the Islet, then branching out, therefore one cell type can have effects on the other cell types.19


Primary regulator of insulin secretion is blood glucose

Insulin is synthesized as a precursor peptide

Preproinsulin: 110a.a.

Proinsulin: 86 a.a., consisting of an A chain, Connecting Peptide, B chain)

2 pairs of basic a.a.'s are cleaved forming insulin and C peptide

stored together in a crystalline structure, both secretes

Secretion occurs in a biphasic manner

First peak occurs when preformed granules are released,

Second peak is from newly synthesized insulin

Insulin receptor: composition

It contains two heterodimers

each containing an alpha subunit (extracellular: recognition site) and

a beta subunit which spans the membrane and contains a tyrosine kinase

Receptor Activation:

insulin binds to alpha subunit

beta subunit increases tyrosine kinase activity, resulting in auto- phosphorylation

Phosphorylated beta subunit promotes aggregation of heterodimers and stabilizes the receptor tyrosine kinase activated state

docking protein (insulin receptor substrate-1, IRS-1) is then phosphorylated

phosphorylated IRS-1 activates other kinases, promoting further phosphorylation reactions

Insulin's second messenger's: these phosphorylation products. Consequence: glucose transporter translocation from sequestered sites to exposure on the cell surface

Insulin-receptor complex is then internalized

Alteration in Insulin receptor affinity:

Decrease affinity: some hormonal agents (e.g. hydrocortisone)

Increase affinity: (excess growth hormone)20

Diabetes mellitus

Diabetes mellitus, often simply referred to as diabetes, is a metabolic disease in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced. This high blood sugar produces the classical symptoms such as polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger).

Type 1 diabetes mellitus (previously insulin dependent diabetes mellitus, IDDM) Juvenile Diabetes is characterized by pancreatic b-cell destruction leading to absolute insulin deficiency. Low IG ratio, high tendency of ketosis/acidosis.

It has two forms:

a. Immune-mediated

b. Idiopathic (i.e. cause unknown), must treat with insulin.

Type 2 diabetes mellitus (non-insulin dependent diabetes mellitus, NIDDM)

Characterized by insulin resistance and relative - rather than absolute - insulin deficiency. Persons with Type 2 diabetes range from:

Predominantly insulin resistant, tending to be obese

Predominantly deficient insulin secretion, less likely to be obese

Gestational diabetes mellitus

This category includes women in whom the onset or recognition of diabetes or IGT occurs first during pregnancy. It does not include diabetic women who become pregnant. GDM occurs in about 3% of pregnancies in western countries. Glucose tolerance usually reverts to normal after delivery. However, the lifetime risk of developing diabetes is increased 3-5 times above normal (i.e., around 20%). Lifestyle measures to reduce progression to diabetes must be stressed.19

Factors contribute in Diabetes Mellitus

Diabetes involves chronic levels of abnormally high glucose (hyperglycemia). Many patients, especially those with type 2 diabetes; also have elevated blood pressure (hypertension), chronic high levels of insulin (hyperinsulinemia) and unhealthy levels of cholesterol and other blood fats (hyperlipidemia). All of these factors contribute to the long-term complications of diabetes, which include:

Vascular disease (diabetic angiopathy), atherosclerosis,heart conditions and stroke

Kidney disease (diabetic nephropathy)

Eye diseases

Nerve damage (diabetic neuropathy)

Impaired thinking

.Infections and wounds


Musculoskeletal disorders

Pregnancy complications

.Emotional difficulties

Insulin shock

Diabetic ketoacidosis

Hyperosmolar hyperglycemic nonketotic state

Syptoms of Untreated Diabetes:

Due to starvation in the midst of plenty, huge level of plasma glucose but none can get into the cell.

Hyperglycemia overloads the kidney, get osmotic diuresis, leading to dehydration and loss of potassium, proteins and fat begin to be broken down for energy:

Leads to ketosis/acidosis

Lean body weight decreases, increased weakness, and decreased immunity

Lack of insulin leaves appetite centers in brain overly stimulated

All this can lead to coma and death due to acidosis, dehydration, and hyperosmolar plasma.20,21


The major components of the treatment of diabetes are:

diet (combined with exercise if possible)

oral hypoglycaemic therapy

insulin treatment

Dietary treatment should aim at:

ensuring weight control

providing nutritional requirements

allowing good glycaemic control with blood glucose levels as close to normal as possible

correcting any associated blood lipid abnormalities

ensuring consistency and compatibility with other forms of treatment if used, for example oral agents or insulin.22

Oral hypoglycemic Agents

These drugs lower blood glucose levels and are effective orally.

i.) Alpha-glucosidase inhibitors: acarbose, miglitol

ii.) Biguanides: metformin

iii.) Meglitinides: repaglinide, nateglinide

iv.) Sulfonylureas

First generation : Tolbutamide, chlorpropamide.

Second generation: glibenclamide, glipizide, gliclazide, glimepiride.

v.) Thiazolidinediones: rosiglitazone, pioglitazone

vi.) A new group called DPP-4 inhibitors


They act on the so called 'sulfonylurea receptors' on the pancreatic β cell membrane- cause depolarization by reducing conductance of ATP sensitive K+ channels. This enhances Ca+2 influxes and causes degranulation. The rate of insulin secretion at any glucose concentration is increased.


Mechanism of action of Biguanides is not clearly understood. They do not cause insulin release, but presence of some insulin is essential for their action.

Suppress hepatic gluconeogenesis and glucose output from liver

Enhancing binding of insulin to its receptors and stimulate insulin mediated glucose disposal.

Interfere with mitochondrial respiratory chain.

Inhibit intestinal absorption of glucose, other hexoses, aminoacids and vit B12.

Alpha-glucosidase inhibitors

They reversibly inhibit α-glucosidases, the final enzymes in the digestion of carbohydrates in the brush border of small intestine mucosa. It slows down and decreases digestion and absorption of polysaccharides and sucrose: postprandial glycaemia is reduced without increasing insulin levels.23


Meglinitides lower blood glucose by stimulating the release of insulin from the pancreas. The mechanism of action involves binding to beta (ß) cells in the pancreatic islets and inhibit ATP-dependent potassium channels in the ß-cell membrane which depolarize the ß-cells. The depolarization of ß-cells leads to the opening of the calcium channels and insulin secretion. The insulin release is glucose-dependent. It diminishes at low glucose concentrations.24


TZDs exert activation of the gamma isoform of the peroxisome proliferator-activated receptor (PPAR gamma), a nuclear receptor. TZD-induced activation of PPAR gamma alters the transcription of several genes involved in glucose and lipid metabolism and energy balance, including those that code for lipoprotein lipase, fatty acid transporter protein, adipocyte fatty acid binding protein, fatty acyl-CoA synthase, malic enzyme, glucokinase and the GLUT4 glucose transporter. TZDs reduce insulin resistance in adipose tissue, muscle and the liver. However, PPAR gamma is predominantly expressed in adipose tissue. Potential signalling factors include free fatty acids (FFA) (well-known mediators of insulin resistance linked to obesity) or adipocyte-derived tumour necrosis factor-alpha (TNF-alpha), which is overexpressed in obesity and insulin resistance.25

DPP-4 inhibitors:

DPP4 inhibitors - Incretin mimetics

Linagliptin is an inhibitor of DPP-4, an enzyme that degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Thus, linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin in a glucose-dependent manner and decreasing the levels of glucagon in the circulation. Both incretin hormones are involved in the physiological regulation of glucose homeostasis. Incretin hormones are secreted at a low basal level throughout the day and levels rise immediately after meal intake. GLP-1 and GIP increase insulin biosynthesis and secretion from pancreatic beta cells in the presence of normal and elevated blood glucose levels. Furthermore, GLP-1 also reduces glucagon secretion from pancreatic alpha cells, resulting in a reduction in hepatic glucose output.26

Insulin treatment

The dose of the insulin preparations is adjusted according to frequent monitoring of blood glucose levels. Blood glucose monitoring should be intensified during intercurrent illness and other stressful conditions and the insulin dose may have to be increased.

Insulin delivery techniques

Plastic disposable syringes with a fixed needle are recommended. They may be reused as long as the needle remains sharp and precautions are taken to prevent contamination. Washing of syringes or wiping the needle with alcohol or any other antiseptic should not be practised. Glass syringes, appropriately sterilized, may be used if plastic syringes are not available.

Other insulin delivery devices may be useful, but are not essential. Insulin injection pens are reliable and easy to use. Pump treatment, providing continuous subcutaneous insulin infusion (CSII), may also be used in some specialized centres, but it is expensive, may cause complications and requires experience and prompt and efficient maintenance facilities which are rarely available in this region.

Implantable insulin pumps are still in the experimental stage.

Injections should be given into the deep subcutaneous tissue at a 45° angle or at a 90° angle when the subcutaneous layer is greater than the needle length.

Rotation of injection sites is recommended to reduce insulin injection site damage.22