1.
The Endocrine Pancreas

3.
The endocrine cells of the pancreas are localized in the islets of Langerhans and constitute only 2% of the mass of the pancreas. The human pancreas contain about 1 million islets of Langerhans which are distributed throughout the organ, but more commonly found in the tail.

4.
<ul><li>The islets are composed of: </li></ul><ul><li>A or α cells (~20%), located at </li></ul><ul><li>the periphery of the islet and secret </li></ul><ul><li>glucagon </li></ul><ul><li>B or β cells (~75%), generally </li></ul><ul><li>located at the center of the islet and </li></ul><ul><li>secret insulin </li></ul><ul><li>D or δ cells (~5%), located </li></ul><ul><li>around the periphery and release </li></ul><ul><li>somatostatin , a paracrine </li></ul><ul><li>inhibitor of both insulin and glucagon </li></ul><ul><li>secretion </li></ul><ul><li>F cells (<2%) produce </li></ul><ul><li>pancreatic polypeptide </li></ul>

5.
Insulin <ul><li>Insulin consists of two peptide chains </li></ul><ul><li>linked by two disulphide bonds </li></ul><ul><li>Insulin is released from the β cells </li></ul><ul><li>by exocytosis in response to an increase </li></ul><ul><li>in blood glucose </li></ul><ul><li>“ half-life” of insulin in circulation </li></ul><ul><li>is about 5 minutes </li></ul><ul><li>Insulin maintains blood glucose </li></ul><ul><li>levels close to 5mmol/L under </li></ul><ul><li>fasting conditions , but may </li></ul><ul><li>temporarily rise as high as </li></ul><ul><li>8 mmol/L after a meal </li></ul><ul><li>Overweight and obese people </li></ul><ul><li>show higher basal levels of insulin </li></ul>

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Regulation of secretion <ul><li>Elevation of plasma glucose concentration directly stimulates: </li></ul><ul><li>- a rapid rise of insulin secretion </li></ul><ul><li>- there is an increase in inreacellular Ca, which is responsible for releasing insulin </li></ul><ul><li>(entry of glucose into β cells does not depend on presence of insulin) </li></ul><ul><li>Insulin secretion by β cells as glucose levels decline </li></ul><ul><li>Increased amono acid concentrations in plasma insulin secretion </li></ul><ul><li>Stimulation of right vagus nerve insulin secretion </li></ul><ul><li>Sympathetic stimulation release of insulin ( α-receptor mechanism ) </li></ul><ul><li>Gastrointestinal hormones (glucagon, gastrin, secretin and gastric inhibitory </li></ul><ul><li>peptide) insulin release </li></ul><ul><li>Keto acids insulin secretion </li></ul><ul><li>Somatostatin, secreted by δ cells insulin secretion </li></ul><ul><li>Drugs (orally active) </li></ul><ul><li>- sulphonylureas (e.g. tolbutamide) insulin secretion </li></ul><ul><li>- glibizide/gliburide insulin secretion and promotes its action at cellular </li></ul><ul><li>level </li></ul><ul><li>- biguanides (e.g. phenformin) act by increasing glucose catabolism </li></ul><ul><li>glucose absorption in the intestine </li></ul><ul><li>- thiazide diuretics insulin secretion </li></ul><ul><li>- diazxide (used in the treatment of hypertension) insulin secretion </li></ul><ul><li>Leptin basal and glucose-stimulated insulin release </li></ul>

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Actions of Insulin <ul><li>Insulin binds to specific membrane receptors and triggers changes in the activity of </li></ul><ul><li>both membrane transport proteins and intracellular enzymes </li></ul><ul><li>Insulin receptor number in starvation and in obesity and acromegaly </li></ul><ul><li>Affinity of insulin receptors in adrenocortical insufficiency but when </li></ul><ul><li>exposed to high glucocorticoid levels </li></ul>

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<ul><li>Insulin blood glucose by facilitating glucose uptake in muscles and adipose </li></ul><ul><li>tissue </li></ul><ul><li>Brain, liver, kidneys, red blood cells & intestinal mucosa are exceptions </li></ul><ul><li>Insulin glycogen synthesis ( glycogenesis ) in the liver & glycogen </li></ul><ul><li>breakdown ( glycogenolysis ) </li></ul><ul><li>Insulin is an anabolic hormone & promotes the rate of protein synthesis by: </li></ul><ul><li>- stimulating amino acid uptake in the liver and skeletal muscle </li></ul><ul><li>- inhibiting protein breakdown </li></ul><ul><li>- inhibiting conversion of amino acids to glucose ( gluconeogenesis ) </li></ul><ul><li>Insulin promotes storage of fat and decreases its utilization by: </li></ul><ul><li>- inhibiting the breakdown of stored lipid ( by hormone-sensitive lipase ) free </li></ul><ul><li>fatty acid levels in circulation </li></ul><ul><li>- stimulating fatty acid synthesis from glucose in the liver </li></ul><ul><li>- promoting glycerol synthesis in lipid cells </li></ul><ul><li>- promoting carbohydrate utilization so that fat is spared ( resting muscle normally </li></ul><ul><li>oxidizes fatty acids for energy ) </li></ul><ul><li>Insulin plasma levels of K ( cellular uptake) </li></ul>

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Clinical <ul><li>Inadequate insulin effect leads to the clinical syndrome of diabetes mellitus </li></ul><ul><li>A primary deficiency of insulin is classified as: type 1/insulin dependent </li></ul><ul><li>(IDDM/juvenile onset diabetes </li></ul><ul><li>- insulin is possibly due to autoimmune destruction of ß cells </li></ul><ul><li>In type 2/non-insulin dependent (NIDMM)/maturity onset diabetes: </li></ul><ul><li>- insulin secretion is relatively unimpaired </li></ul><ul><li>- insulin effect on the cells are inhibited/insulin resistance </li></ul><ul><li>- mostly found in elderly, overweight patients </li></ul><ul><li>Occasionally, diabetes mellitus is secondary to excess secretion of a diabetogenic </li></ul><ul><li>hormone , e.g. cortisol, growth hormone or very rarely, glucagon . </li></ul>

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Symptoms and biochemical abnormalities <ul><li>Hypergycemia </li></ul><ul><li>- decreased glucose uptake & utilization plasma glucose level </li></ul><ul><li>Glucosuria </li></ul><ul><li>- plasma glucose ~11 mmol/L crosses renal T max limit excreted in urine </li></ul><ul><li>Polyuria </li></ul><ul><li>- glucose within the renal tubules osmotic retention of H2O urine </li></ul><ul><li>production ( osmotic diuresis ) </li></ul><ul><li>Polydipsia </li></ul><ul><li>- polyuria dehydration thirst and drinking </li></ul><ul><li>Reduction in amino acid uptake protein synthesis negative nitrogen </li></ul><ul><li>balance impaired growth ( in children )/muscle wasting & weight loss ( in </li></ul><ul><li>adults ) </li></ul><ul><li>Lipid mobilization plasma free fatty acid levels weight loss </li></ul><ul><li>Ketosis </li></ul><ul><li>- ß-oxidation of fatty acid ketone bodies metabolic acidosis </li></ul><ul><li>Increased ventilation </li></ul><ul><li>- respiratory compensation of acidosis </li></ul>

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Treatment <ul><li>If the patient remain untreated, diabetes mellitus will eventually lead to ketotic </li></ul><ul><li>coma and death from dehydration and acidosis </li></ul><ul><li>- recombinant insulin treatment can lead to a good control of glucose levels. </li></ul><ul><li>Cases in which hyperglycemia is associated with obesity , diet alone or diet in </li></ul><ul><li>combination with physical exercise may be adequate </li></ul><ul><li>Excess insulin hypoglycemia sympathetic activity </li></ul><ul><li>tremor, sweating, heart rate, anxiety, may coma , could reversed by </li></ul><ul><li>intravenous glucose / glucagon </li></ul>

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Glucagon <ul><li>Glucagon is a catabolic peptide hormone secreted by α cells of the pancreatic islets </li></ul>Regulation of secretion <ul><li>Glucagon secretion is directly stimulated by: </li></ul><ul><li>- low blood glucose concentration </li></ul><ul><li>- high levels of circulating amino acids </li></ul><ul><li>Somatostatin glucagon secretion </li></ul><ul><li>Insulin & secretin glucagon secretion </li></ul><ul><li>Sympathetic stimulation glucagon secretion ( ß-receptor mechanism ) </li></ul><ul><li>Vagal stimulation glucagon secretion </li></ul><ul><li>All forms of physical stress glucagon secretion </li></ul>

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Actions of glucagon <ul><li>Glucagon effects oppose those of insulin, most pronounced in the liver to </li></ul><ul><li>safeguard against hypoglycemia </li></ul><ul><li>Glucagon increases blood glucose levels by: </li></ul><ul><li>- glycogenolysis in the liver ( phosphorylase) </li></ul><ul><li>- protein breakdown in muscle </li></ul><ul><li>- protein synthesis in the liver </li></ul><ul><li>- formation of glucose from amino acids and glycerol ( gluconeogenesis) </li></ul><ul><li>- fat mobilization ( hormone-sensitive lipase activity) free fatty </li></ul><ul><li>acids in blood ( ß-oxidation ) keto acid formation </li></ul>

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Somatostatin <ul><li>Somatostatin is a peptide hormone secreted by δ cells of the </li></ul><ul><li>pancreatic islets (also produced in the hypothalamus ) in response to: </li></ul><ul><li>- blood glucose </li></ul><ul><li>- plasma amino acids </li></ul><ul><li>- fatty acids </li></ul><ul><li>Somatostatin decreases gastrointestinal functions by: </li></ul><ul><li>- motility </li></ul><ul><li>- secretion </li></ul><ul><li>- absorption </li></ul><ul><li>Somatostatin splanchnic blood flow </li></ul><ul><li>Somatostatin release of: </li></ul><ul><li>- insulin </li></ul><ul><li>- glucagon </li></ul>

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Amylin <ul><li>A pancreatic hormone , is stored in the ß cells and released together </li></ul><ul><li>with insulin </li></ul><ul><li>Amylin is a potent inhibitor of gastric emptying </li></ul><ul><li>Amylin insulin secretion </li></ul><ul><li>It can induce insulin resistance </li></ul>