Insulin

Insulin (Latin insula, "island", as it is produced in the Islets of Langerhans in the pancreas) is a polypeptide hormone that regulates carbohydrate metabolism. Apart from being the primary effector in carbohydrate homeostasis, it also has a substantial effect on small vessel muscle tone, controls storage and release of fat (triglycerides) and cellular uptake of both amino acids and some electrolytes. In this last sense, it has anabolic properties. Its concentration (more or less, prsence or absence) has extremely widespread effects throughout the body.

Regulatory action on blood glucose

Despite long intervals between meals or the occasional consumption of meals with a substantial carbohydrate load (e.g., half a birthday cake or a bag of potato chips), human blood glucose levels normally remain within a narrow range. In most humans this varies from about 70 mg/dl to perhaps 110 mg/dl (3.9 to 6.1 mmol/litre) except shortly after eating when the blood glucose level rises temporarily. In a healthy adult male of 75 kg with a blood volume of 5 litre, a blood glucose level of 100 mg/dl or 5.5 mmol/l corresponds to about 5 g (1/5 ounce) of glucose in the blood and approximately 45 g (1 1/2 ounces) in the total body water (which obviously includes more than merely blood and will be usually about 60% of the total body weight in men). This homeostatic effect is the result of many factors, of which hormone regulation is the most important.

Related Topics:
Carbohydrate - Birthday cake - Potato chip - Blood glucose - Mmol - Kg - Blood - Litre - Body water - Body weight - Homeostatic

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There are two groups of mutually antagonistic metabolic hormones affecting blood glucose levels:

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• catabolic hormones (such as glucagon, growth hormone, and catecholamines), which increase blood glucose
• and one anabolic hormone (insulin), which decreases blood glucose

Mechanisms which restore satisfactory blood glucose levels after hypoglycemia must be quick and effective because of the immediate serious consequences of insufficient glucose. This is because, at least in the short term, it is far more dangerous to have too little glucose in the blood than too much. In healthy individuals these mechanisms are indeed generally efficient, and symptomatic hypoglycemia is generally only found in diabetics using insulin or other pharmacologic treatment. Such hypoglycemic episodes vary greatly between persons and from time to time, both in severity and swiftness of onset. In severe cases prompt medical assistance is essential, as damage (to brain and other tissues) and even death will result from sufficiently low blood glucose levels.

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Beta cells in the islets of Langerhans are sensitive to variations in blood glucose levels through the following mechanism (see figure to the right):

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• Glucose enters the beta cells through the glucose transporter GLUT2
• Glucose goes into the glycolysis and the respiratory cycle where the high-energy ATP molecule is produced by oxidation
• Dependent on blood glucose levels and hence ATP levels, the ATP controlled potassium channels (K+) close and the cell membranes depolarise
• On depolarisation, voltage controlled calcium channels (Ca2+) open and calcium flows into the cells
• An increased calcium level causes activation of phospholipase C, which cleaves the membrane phospholipid phosphatidyl inositol 4,5-bisphosphate into inositol 1,4,5-triphosphate and diacylglycerol.
• Inositol 4,5-biphosphate binds to receptor proteins in the membrane of endoplasmic reticulum. This further raises the cell concentration of calcium.
• Significantly increased amount of calcium in the cells causes release of previously synthesised insulin, which has been stored in secretory vesicles
• The calcium level also regulates expression of the insulin gene via the calcium responsive element binding protein (CREB).

This is the main mechanism for release of insulin and regulation of insulin synthesis. In addition some insulin synthesis and release takes place generally at food intake, not just glucose or carbohydrate intake, and the beta cells are also somewhat influenced by the autonomic nervous system.

Related Topics:
Carbohydrate - Autonomic nervous system

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Substances that stimulate insulin release are also acetylholin, released from vagus nerve endings (parasympathetic nervous system), cholecystokinin, released by enteroendocrine cells of intestinal mucosa and gastrointestinal inhibitory peptide (GIP). The first of these act similarly as glucose through phospholipase C, while the last one acts through the mechanism of adenylate cyclase.

Related Topics:
Parasympathetic nervous system - Cholecystokinin - Enteroendocrine cell - Intestinal mucosa - Gastrointestinal inhibitory peptide - Adenylate cyclase

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Sympathetic nervous system (α2 adrenergic agonists) inhibits the release of insulin.

Related Topics:
Sympathetic nervous system - α₂ adrenergic agonists

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When the glucose level comes down to the usual physiologic value, insulin release from the beta cells slows or stops. If blood glucose levels drop lower than this, especially to dangerously low levels, release of hyperglycemic hormones (most prominently glucagon from Islet alpha cells) forces release of glucose into the blood from cellular stores. The release of insulin is strongly inhibited by the stress hormone adrenalin (epinephrine).

Related Topics:
Stress hormone - Adrenalin

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