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Physiologic Effects of Glucagon: Glucagon is to stimulate an increase in blood concentration of glucose.
Glucagon exerts control over Two metabolic pathways within the liver: gon stimulates breakdown of
glycogen stored in the liver. When blood glucose levels begin to fall, glucagon is secreted and acts on
hepatocytes to activate the enzymes that depolymerize glycogen and release glucose. Glucagon
activates hepatic gluconeogenesis. Gluconeogenesis is the pathway by which non hexose substrates
such as amino acids are converted to glucose. Glucagon also appears to have a minor effect of
enhancing lipolysis of triglyceride in adipose tissue which could be viewed as an addition means of
conserving blood glucose by providing fatty acid fuel to most cells. Glucagon is secreted in response to
hypoglycemia or low blood concentrations of glucose. Two other conditions are known to trigger
glucagon secretion Elevated blood levels of amino acids, as would be seen after consumption of a
protein-rich meal, In this situation, glucagon would foster conversion of excess amino acids to glucose
by enhancing gluconeogenesis. High blood levels of amino acids also stimulate insulin release, this would
be a situation in which both insulin and glucagon are active
Exercise: In this case, it is not clear whether the actual stimulus is exercise per se, or the accompanying
exercise-induced depletion of glucose Disease States Diseases associated with excessively high or low
secretion of glucagon are fare Cancers of alpha cells (glucagonomas) are one situation known to cause
excessive glucagon secretion. though insulin deficiency is clearly the major defect in type diabetes
mellitus, There is a considerable evidence that aberrant secretion of glucagon contributes to the
metabolic derangements seen in this important disease. For example, many diabetic patients with
hyperglycemia also have elevated blood concentrations of glucagon, but glucagon secretion is normally
suppressed by elevated levels of blood glucose oma tostatin Somatostatin was first discovered in
hypothalamic extracts that inhibited secretion of growth hormone. Somatostatin was found to be
secreted by a broad range of tissues, including :pancreas, intestinal tract and nervous system outside
the hypothalamus Structure and Synthesis,Two forms of somatostatin are synthesized. They are referred
to as SS-14 and SS-28, reflecting their amino acid chain length. Both forms earape of prosomatostatin,
which itself
referred to as SS-28, reflecting their amino acid chain length. Both forms of are generated by proteolytic
cleavage of prosomatostatin, which itself is derived from preprosomatostatin. Two cysteine residules in
SS-14 allow the peptide to form an internal disulfide bond proteolytic cleavage sites signal peptide
cleavage Preprosomatostatin Prosomatostatin SS-28 SS-14.
Cthe relative amounts of SS-14 versus SS-28 secreted depend upon the tissue. For example, SS-14 is
produced in the nervous system and from pancreas, SS-28 from the intestine secretes SS- 14 and SS-28,
have different biological potencies: 8 is roughly ten-fold more potent in inhibition of growth hormone
secretion, 4 is less potent in inhibiting glucagon release. Receptors and Mechanism of Action: Five
stomatostatin receptors have been identified and characterized, all of which are members of the G
protein-coupled receptor superfamily. Each of the receptors activates distinct signalling mechanisms
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within cells, although all inhibit aden cyclase. Four of the five receptors do not differentiate SS-14 from
SS-28 Physiologic Effects: Somatostatin acts by both endocrine and paracrine pathways to affect its
target cells. A majority of the circulating somatostatin appears to come from the pancreas and
gastrointestinal tract. Effects on the Pituitary Gland; Somatostatin was inhibits the secretion of growth
hormone from the pituitary gland Experimentally, growth hormone secretion is suppressed by
somatostatin administration Effects on the Pancreas,Cells within pancreatic islets secrete insulin,
glucagon and somatostatin Somatostatin appears to act primarily in a paracrine manner to inhibit the
secretion of both insulin and glucagon. It also has the effect in suppressing pancreatic exocrine
secretions, by inhibiting cholecy stokinin-stimulated enzyme secretion and secretin-stimulated
bicarbonate secretion. Effects on the Gastrointestinal Tract. Somatostatin is secreted in the Gl
epithelium, and by neurons in the centeric nervous system. Somatostatin is inhibit secretion of many GI
hormones, including: gastrin, cholecystokinin, secretin and vasoactive intestinal peptide. Somatostatin
suppresses secretion of gastric acid and pepsin, lowers the rate of gastric emptying, and reduces smooth
muscle contractions and reduce blood flow within the intestine
These activities seem to have the overall effect of decreasing the rate of nutrient absorption. Effects on
the Nervous System, Somatostatin is often have a Neuromodulatory activity within the central nervous
sytem, and Complex effects on neural transmission. Injection of somatostatin into the brain of rodents
leads to: Increased arousal and decreased sleep, and Impairment of some motor responses.
Pharmacologic Uses; Somatostatin and its synthetic ad
In terms of negative control, glucagon secretion is inhibited by high levels of blood glucose.
It is not clear whether this reflects a direct effect of glucose on the alpha cell, or perhaps an
effect of insulin, which is known to dampen glucagon release. Another hormone well known
to inhibit glucagon secretion is somatostatin.