Glucagon Glucagonic Fitness Glucose Cure

Glucagon Glucagonic Fitness Glucose Cure

Glucagon is an important hormone involved in carbohydrate metabolism. Produced by the pancreas, it is released when the glucose level in the blood is low (HYPOglycemia), causing the liver to convert stored glycogen into glucose and release it into the bloodstream. The action of glucagon is thus opposite to that of insulin, which instructs the body's cells to take in glucose from the blood in times of satiation.

Production

The hormone is synthesized and secreted from alpha cells (α-cells) of the islets of Langerhans, which are located in the endocrine portion of the pancreas. In rodents, the alpha cells are located in the outer rim of the islet. Human islet structure is much less segregated, and alpha cells are distributed throughout the islet.

Regulatory mechanism

Increased secretion of glucagon is caused by:

* Decreased plasma glucose
* Increased catecholamines - norepinephrine and epinephrine
* Increased plasma amino acids (to protect from hypoglycemia if an all protein meal is consumed)
* Sympathetic nervous system
* Acetylcholine
* Cholecystokinin

Decreased secretion of glucagon (inhibition) is caused by:

* Somatostatin
* Insulin

Function

Glucagon helps maintain the level of glucose in the blood by binding to glucagon receptors on hepatocytes, causing the liver to release glucose - stored in the form of glycogen - through a process known as glycogenolysis. As these stores become depleted, glucagon then encourages the liver to synthesize additional glucose by gluconeogenesis. This glucose is released into the bloodstream. Both of these mechanisms lead to glucose release by the liver, preventing the development of hypoglycemia. Glucagon also regulates the rate of glucose production through lipolysis.

* Increased free fatty acids and ketoacids into the blood
* Increased urea production

Mechanism of action

Glucagon binds to the glucagon receptor, a G protein-coupled receptor located in the plasma membrane. The conformation change in the receptor activates G proteins, a heterotrimeric protein with α, β, and γ subunits. The subunits breakup as a result of substitution of a GDP molecule with a GTP mol, and the alpha subunit specifically activates the next enzyme in the cascade, adenylate cyclase.

Adenylate cyclase manufactures cAMP (cyclical AMP) which activates protein kinase A (cAMP-dependent protein kinase). This enzyme in turn activates phosphorylase kinase, which in turn, phosphorylates glycogen phosphorylase, converting into the active form called phosphorylase A. Phosphorylase A is the enzyme responsible for the release of glucose-1-phosphate from glycogen polymers.

Endocrinology. 1996 Aug;137(8):3193-9.

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Glucagon response to HYPOglycemia is improved by insulin-independent restoration of normoglycemia in diabetic rats.

Shi ZQ, Rastogi KS, Lekas M, Efendic S, Drucker DJ, Vranic M.

Department of Physiology, Faculty of Medicine, University of Toronto, Ontario, Canada.

The aim of this study was to determine whether the impaired glucagon response to insulin-induced hypoglycemia in the diabetic rat can be improved by correction of hyperglycemia independent of insulin.

Four groups of age-matched male Sprague-Dawley rats (246 +/- 13 g BW) were studied: 1) normal controls (NC; n = 7); 2) diabetic, untreated (DU; n = 6); 3) diabetic, treated for 5-7 days using sustained release (2-3 U/day) insulin implants (DI; n = 6); and 4) diabetic, treated for 3-4 days with phlorizin (0.4 g/kg), given sc twice daily (DP; n = 7). Diabetes was induced by a single injection of streptozotocin (65 mg/kg). Basal plasma glucose was 7.4 +/- 0.3 mM in NC, but rose to 14.5 +/- 2.2 mM in DU.

Basal hyperglycemia was corrected with phlorizin and insulin treatments (5.5 +/- 0.5 and 6.7 +/- 0.8 mM, respectively). NC rats responded to insulin-induced hypoglycemia with a rapid and marked increase in glucagon (peak, 2059 +/- 311 pg/ml). The glucagon response was blunted in DU (635 +/- 180 pg/ml) and was partially improved by prolonged normalization of glycemia in DP (1335 +/- 295 pg/ml; P <>

Treatment with both insulin and phlorizin reversed the changes in the pancreatic content of both glucagon and somatostatin. Pancreatic proglucagon messenger RNA did not show significant differences among the four groups in either state. Insulin treatment in the DI group resulted in a delayed and much smaller increase in the glucagon response (740 +/- 138 pg/ml) to hypoglycemia despite normalization of glycemia.

We, therefore, conclude that in streptozotocin-diabetic rats, the impaired glucagon responsiveness to hypoglycemia is significantly improved by insulin-independent correction of hyperglycemia, suggesting the importance of normoglycemia per se in maintaining, at least in part, the glucose sensitivity of pancreatic alpha-cells.

Endocrinology. 1998 Nov;139(11):4540-6.

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Insulin, but not glucose lowering corrects the hyperglucagonemia and increased proglucagon messenger ribonucleic acid levels observed in insulinopenic diabetes.

Dumonteil E, Magnan C, Ritz-Laser B, Meda P, Dussoix P, Gilbert M, Ktorza A, Philippe J.

Department of Medicine, Centre Médical Universitaire, Geneva, Switzerland.

The factors that regulate glucagon biosynthesis and proglucagon gene expression are poorly defined. We previously reported that insulin inhibits proglucagon gene expression in vitro.

In vivo, however, the effects of insulin on the regulation of the proglucagon gene have been controversial. Furthermore, whether glucose plays any role alone or in conjunction with insulin on proglucagon gene expression is unknown.

We investigated the consequences of insulinopenic diabetes on glucagon gene expression in the endocrine pancreas and intestine and whether insulin and/or glucose could correct the observed abnormalities.

We show here that in the first 3 days after induction of hyperglycemia by streptozotocin, rats have levels of plasma glucagon and proglucagon messenger RNA comparable to those of normoglycemic controls despite hyperglycemia.

With more prolonged diabetes, plasma glucagon and proglucagon messenger RNA levels increase; this increase is corrected by insulin treatment, but not by phloridzin despite normalization of the glycemia by both treatments.

Proglucagon gene expression exhibits the same regulatory response to glucose and insulin in both pancreas and ileum.

We conclude that insulin tonically inhibits proglucagon gene expression in the pancreas and ileum and that glucose plays a minor, if any, role in this regulation.

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Energy drinks safety questioned by German agency

By Shane Starling

http://www.NutraIngredients-usa.com/news/ng.asp?n=85729-red-bull-federal-institute-for-risk-assessment-energy-drinks-taurine-caffeine

05-Jun-2008 - Energy drinks have the potential to cause liver damage, heart failure and even death and should carry warnings for certain population groups, according to a German body.

The Federal Institute for Risk Assessment (BfR) analysed various human trials conducted over recent years that noted cardiac dysrhythmia, seizures, kidney failure and fatalities occurred after consuming energy drinks.

It called for tighter labelling to warn consumers of potential health hazards.

BfR said it had repeatedly advocated the use of warning labels for demographic sub-groups such as children, pregnant women, lactating women and caffeine-sensitive individuals, who should refrain from using energy drinks.

It said consumers with high blood pressure and heart disease should restrict energy drink use and called for more "robust studies".

Warnings about the use of energy drinks such as Red Bull with intensive physical activity or alcoholic beverages should also be mandatory.

BfR noted the regularity with which energy drinks were mixed with alcoholic beverages meant "persons no longer realistically assess their dwindling responsiveness caused by alcohol consumption under the influence of energy drinks", a problem the energy drinks sector had never taken full responsibility for.

Such label warning were in place in countries like Finland and Canada, ingredient limitations were in place in France where taurine is banned.

Denmark and Norway had banned or recommended banning energy drinks altogether.

BfR's review took in products containing not more than 320 mg/l of caffeine, 4000 mg/l of taurine, 200 mg/l of inosite and 2400 mg/l of glucuronolactone.

Consumption hazards

It noted that as far back as 2002 a scan of German poison information and treatment centres revealed energy drink-related incidents included seizures, tachycardia (increased heart rate), cardiac dysrhythmia, rhabdomyolysis (decline of skeletal muscle cells), agitation, hypertonia (high blood pressure), respiratory disorders and psychotic conditions.

As well as citing numerous studies demonstrating the potential hazards of energy drink consumption due to different ingredients, BfR's report notes a number of case studies where energy drinks have led to adverse reactions including death in combination with alcohol and alone.

The use of energy drinks as substitutes for sports beverages was also questioned. Sports beverages supplied, "calorific energy, are consumed in larger amounts in conjunction with intensive physical activity and are, therefore, associated with the consumer conditions which are specifically contra-indicated for energy drinks."

The European Food Safety Authority (EFSA) is in the process of assessing the status of energy drinks, with an EU-wide approach a possible consequence of that assessment.

"This could encourage EU-wide data matching and lead to the emergence of new findings about consumer groups who may be particularly sensitive to energy drinks," Bfr said. "As far as exposure is concerned, it is pointed out that in a Scientific Committee on Food (SCF) expert report which is still valid, reference was made to the unit of 250 ml cans for energy drinks which had been the norm up to then whereas far larger packs are now sold internationally."