Insulin overproduction

It should be mentioned that the inhibition of superoxide overproduction and lipid peroxidation by lipoic acid has been recently shown in animal models of diabetes mellitus. The administration of LA to streptozotocin-diabetic rats suppressed the formation of lipid peroxidation products [213], In another study the supplementation of glucose-fed rats with lipoic acid suppressed aorta superoxide overproduction as well as an increase in blood pressure and insulin resistance [214]. 

Theoretically, diabetes could be as readily caused by overproduction of the pituitary hormone as by the underproduction of insulin. Actually both activities probably vary greatly, and the diabetes results from an imbalance. Even when diabetes has its origin in an overactivity of the pituitary in producing the diabetogenic hormone, insulin may still be an effective remedy. Actually, of course, diabetes is sometimes insulin-resistant, which fact reveals that the disease does not always have the same origin. 

Metformin, a biguanide derivative, can lower excessive blood glucose levels, provided that insulin is present Metformin does not stimulate insulin release. Glucose release from the liver is decreased, while peripheral uptake is enhanced. The danger of hypoglycemia apparently is not increased. Frequent adverse effects include anorexia, nausea, and diarrhea Overproduction of lactic acid (lactate acidosis, lethality 50%) is a rare, potentially fatal reactioa Metformin is used in combination with sulfony-lureas or by itself. It is contraindicated in renal insufficiency and should therefore be avoided in elderly patients. 

Failure of Insulin to suppress gluconeogenesis in liver leads to overproduction of new glucose, which exacerbates the elevation of blood glucose due to decreased uptake of dietary glucose by muscle and adipose. 

Individuals with either type of diabetes are unable to take up glucose efficiently from the blood recall that insulin triggers the movement of GLUT4 glucose transporters to the plasma membrane of muscle and adipose tissue (see Fig. 12-8). Another characteristic metabolic change in diabetes is excessive but incomplete oxidation of fatty acids in the liver. The acetyl-CoA produced by JS oxidation cannot be completely oxidized by the citric acid cycle, because the high [NADH]/[NAD+] ratio produced by JS oxidation inhibits the cycle (recall that three steps convert NAD+ to NADH). Accumulation of acetyl-CoA leads to overproduction of the ketone bodies acetoacetate and /3-hydroxybutyrate, which cannot be used by extrahepatic tissues as fast as they are made in the liver. In addition to /3-hydroxybutyrate and acetoacetate, the blood of diabetics also contains acetone, which results from the spontaneous decarboxylation of acetoacetate ... 

Glucagon exerts a ketogenic action on the liver which is more pronounced in insulin-deficient states. This action is thought to be due mainly to the inhibition of acetyl-CoA carboxylase with resulting decrease in malonyl-CoA. Malonyl-CoA is an inhibitor of carnitine acyltransferase I which is the rate-limiting step for mitochondrial fatty acid oxidation. A decrease in malonyl-CoA is thus postulated to lead to overproduction of acetyl-CoA which is then condensed to form ketone bodies. 

Does insulin correct the overproduction of glucose in the liver ... 

Cancer is a disease involving an increased rate of division and muitiplicaticm of a particular type of cell. In one type of cancer, an increased n imber of l-cc]ls in the pancreas may result in overproduction of insulin. Would you expect the brain to have a deficient or overabundant Supply of energy (See Townsend and Thompson (19S5).)... 

The glucagon/insulin ratio can rise under certain pathological conditions (i.e., insulin-dependent diabetes). A small percentage of diabetics develop ketoacidosis, a condition that results from the overproduction and underuhlization of ketone bodies. Increased concentrations of p hydmxybutyrate and acetoacetate, which are acids, can cause a drop in the pH of the blood. This acidification, known as acidosis, can impair the ablLity of the heart to contract and result in a loss of consciousness and coma, which, in rare cases, may be fatal. Diabetic ketoacidosis may manifest as abdominal pain, nausea, and vomiting. A subject may hyperventilate (breathe quickly and deeply) to correct acidosis, as described under Sodium, Potassium, and Water in Chapter 10. It is the responsibility of the clinician, when confronted with a subject whose breath smells of acetone or who is hyperventilating, to facilitate prompt treatment. 

Failure of the serum cortisol to rise after insulin-induced hypoglycaemia is also a characteristic feature of Cushing s syndrome. Since patients with cortisol overproduction will be insulin-resistant, adequate hypoglycaemia may not be achieved with O.l, ) units of insulin/kg body weight. A higher dose may have to be u.sed. In normal individuals a fall of blood glucose concentration to less than... 

Metabolic regulation of VLDL secretion overproduction in insulin-resistant states. 525... 

There is evidence that intestinal lipoprotein production is increased in diabetes and insulin-resistant states. Intestinal lipoprotein overproduction has been suggested to be a major contributor to the fasting and postprandial lipemia observed in insulin-resistant states (M.R. Taskinen, 2003). Evidence for increased formation of intestinal apo B48-containing lipoproteins as a result of insulin resistance comes from studies in animal models (K. Adeli, 2006) as well as humans. The underlying mechanisms are currently unknown, but increased de novo lipogenesis, reduced apo B48 degradation, and higher MTP expression have been implicated. 

Insulin normally inhibits lipolysis by decreasing the lipolytic activity of HSL in the adipocyte. Individuals such as Di Abietes, who have a deficiency of insulin, have an increase in lipolysis and a subsequent increase in the concentration of free fatty acids in the blood. The liver, in turn, uses some of these fatty acids to synthesize triacylglycerols, which then are used in the hepatic production of VLDL. VLDL is not stored in the liver but is secreted into the blood, raising its serum concentration. Di also has low levels of LPL because of decreased insulin levels. Her hypertriglyceridemia is the result, therefore, of both overproduction of VLDL by the liver and decreased breakdown of VLDL triacylglycerol for storage in adipose cells. 

Hormones are messengers that influence how tissues, organs, and other parts of your body function. An overproduction of hormones causes an overreaction such as growing too tall. An underproduction of hormones causes an underreaction such as producing insufficient insulin to metabolize glucose. 

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