Hepatic glucose production

Metformin restrains hepatic glucose production principally by suppression of gluconeogenesis. The mechanisms involve potentiation of insulin action and decreased hepatic extraction of certain gluconeogenic substrates such as lactate. In addition, metformin reduces the rate of hepatic glycogenolysis and decreases the activity of hepatic glucose-6-phosphatase. Insulin-stimulated glucose uptake and glycogenesis by skeletal muscle is increased by metformin mainly by increased... 

Antidiabetic Drugs other than Insulin. Figure 3 The antihyperglycaemic effect of metformin involves enhanced insulin-mediated suppression of hepatic glucose production and muscle glucose uptake. Metformin also exerts non-insulin-dependent effects on these tissues, including reduced fatty acid oxidation and increased anaerobic glucose metabolism by the intestine. FA, fatty acid f, increase i decrease. 

Biological actions Adipocyte differentiation fatty acid uptake lipogenesis glucose uptake other effects on nutrient metabolism which lower hepatic glucose production... 

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... 

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

Alcohol Reduction Reduces hepatic glucose production... 

Metformin improves glucose tolerance in NIDDM subjects by lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity (increases peripheral glucose uptake and utilization). 

Glucose control Increased hepatic glucose production and glucose intolerance in hyperthyroidism impaired insulin action and glucose disposal in hypothyroidism... 

Insulin resistance is the decreased ability of target tissues, such as liver, adipose, and muscle, to respond properly to normal circulating concentrations of insulin. For example, insulin resistance is characterized by uncontrolled hepatic glucose production, and decreased glucose uptake by muscle and adipose tissue. 

Biguanides Metformin (Glucophage) Act directly on the liver to decrease hepatic glucose production also increase sensitivity of peripheral tissues (muscle) to insulin Gastrointestinal disturbances lactic acidosis may also occur in rare cases, and this effect can be severe or fatal... 

Consoli, A., Nuijhan, N., Capani, F., and Gerich, J. 1989. Predominant role of gluconeo-genesis in increased hepatic glucose production in NIDDM. Diabetes 38, 550-557. 

When studied under more controlled conditions using the eug-lycemic hyperinsulinemic clamp method, it is apparent that chronic treatment of insulin-resistant rats with PPARy agonists can substantially improve peripheral insulin-stimulated glucose disposal and the ability of insulin to suppress hepatic glucose production (67, 71, 72). 

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