Insulin Liver

These enzymes, which mainly catalyze hydrolytic reactions, have the zinc ions at their active sites. However, Zn ions also appear necessary in some cases for stabilization of the protein structure, e.g. in Cu/Zn SOD, insulin, liver alcohol dehydrogenase and alkaline phosphatases. 

Insulin Liver Increased glucokinase increased glucose uptake Increased glycogen synthase activity glycogen deposition Inhibited gluconeogenesis Increased malic enzyme, acetyl-CoA carboxylase, fatty acid synthetase and stearoylCoA desaturase increased lipogenesis Release of VLDL from hepatocytes... 

Insulin Liver, skeletal muscle, adipose tissue, renal medulla... 

Insulin is a peptide hormone, secreted by the pancreas, that regulates glucose metabolism in the body. Insufficient production of insulin or failure of insulin to stimulate target sites in liver, muscle, and adipose tissue leads to the serious metabolic disorder known as diabetes mellitus. Diabetes afflicts millions of people worldwide. Diabetic individuals typically exhibit high levels of glucose in the blood, but insulin injection therapy allows diabetic individuals to maintain normal levels of blood glucose. 

Usual dose schedules of streptozotocin involve 500 mg/m2 i.v. during five consecutive days. The major toxicity is renal tubular damage. Treatment of metastatic insulinomas may result in the release of insulin from the tumor and subsequent hypoglycemic coma. Less severe toxicities include diarrhea, anemia, and mild alterations in glucose tolerance or liver function tests. 

There is weak expression of PPARy in muscle, liver and other tissues, enabling TZDs to support the effects of insulin in these tissues, notably increased glucose uptake in muscle and reduced glucose production in liver. TZDs may also affect nutrient metabolism by skeletal muscle through a direct mitochondrial action that is independent of PPARy. 

Prandial insulin releasers (meglitinides) Severe liver or renal disease0 Hypoglycaemiad b... 

The first hormonal signal found to comply with the characteristics of both a satiety and an adiposity signal was insulin [1]. Insulin levels reflect substrate (carbohydrate) intake and stores, as they rise with blood glucose levels and fall with starvation. In addition, they may reflect the size of adipose stores, because a fatter person secretes more insulin than a lean individual in response to a given increase of blood glucose. This increased insulin secretion in obesity can be explained by the reduced insulin sensitivity of liver, muscle, and adipose tissue. Insulin is known to enter the brain, and direct administration of insulin to the brain reduces food intake. The adipostatic role of insulin is supported by the observation that mutant mice lacking the neuronal insulin receptor (NDRKO mice) develop obesity. 

GLUT2 is a glucose/fructose transport facilitator expressed in liver, small intestine, kidney, and pancreatic p-cells. GLUT2 has low-affinity for glucose (Km= 60 mM) and fructose (ivm=65 mM), and is an essential part of the glucose sensor of pancreatic (3-cells which controls insulin secretion and biosynthesis. 

The insulin-binding domain of the INSR is located within a cystein-rich region of the a-subunits. Alternative splicing of exon 11 generates two isoforms of the a-subunit which differ in their C-terminus and in their tissue distribution (type A leukocytes type B liver type A and B skeletal muscle and fat). The isoforms differ in their affinity to insulin (A > B), but then-relevance for normal and impaired insulin action is not entirely clear [1,2]. 

Taken together, these data emphasize the importance of insulin action in the liver for glucose homeostasis, in the regulation of insulin secretion from (3-cells and indicate that the INSR plays an important role in the central regulation of body weight and reproduction [4, 5]. 

Insulin resistance occurs when the normal response to a given amount of insulin is reduced. Resistance of liver to the effects of insulin results in inadequate suppression of hepatic glucose production insulin resistance of skeletal muscle reduces the amount of glucose taken out of the circulation into skeletal muscle for storage and insulin resistance of adipose tissue results in impaired suppression of lipolysis and increased levels of free fatty acids. Therefore, insulin resistance is associated with a cluster of metabolic abnormalities including elevated blood glucose levels, abnormal blood lipid profile (dyslipidemia), hypertension, and increased expression of inflammatory markers (inflammation). Insulin resistance and this cluster of metabolic abnormalities is strongly associated with obesity, predominantly abdominal (visceral) obesity, and physical inactivity and increased risk for type 2 diabetes, cardiovascular and renal disease, as well as some forms of cancer. In addition to obesity, other situations in which insulin resistance occurs includes... 

Insulin is a hormone manufactured by the beta cells of the pancreas. It is the principal hormone required for the proper use of glucose (carbohydrate) by the body. Insulin also controls the storage and utilization of amino acids and fatty acids. Insulin lowers blood glucose levels by inhibiting glucose production by the liver. 

Insulin appears to activate a process that helps glucose molecules enter the cells of striated muscle and adipose tissue Figure 49-1 depicts normal glucose metabolism. Insulin also stimulates die synthesis of glycogen by die liver. In addition, insulin promotes protein syntiiesis and helps the body store fat by preventing its breakdown for energy. 

Metformin sensitizes die liver to circulating insulin levels and reduces hepatic glucose production. 

The rate of mitochondrial oxidations and ATP synthesis is continually adjusted to the needs of the cell (see reviews by Brand and Murphy 1987 Brown, 1992). Physical activity and the nutritional and endocrine states determine which substrates are oxidized by skeletal muscle. Insulin increases the utilization of glucose by promoting its uptake by muscle and by decreasing the availability of free long-chain fatty acids, and of acetoacetate and 3-hydroxybutyrate formed by fatty acid oxidation in the liver, secondary to decreased lipolysis in adipose tissue. Product inhibition of pyruvate dehydrogenase by NADH and acetyl-CoA formed by fatty acid oxidation decreases glucose oxidation in muscle. 

In addition to the direct effects of hyperglycemia in enhancing the uptake of glucose into the liver, the hormone insulin plays a central role in regulating blood glucose. It is produced by the B cells of the islets of Langerhans in the pancreas in response to hyperglycemia. The B islet cells are freely permeable to glu-... 

Insulin is secreted as a direct response to hyperglycemia it stimulates the liver to store glucose as glycogen and facilitates uptake of glucose into extra-hepatic tissues. 

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