Hepatic glucose

The increase in insulin concentrations produced by sulphonylureas lowers blood glucose concentrations through decreased hepatic glucose output and increased glucose utilisation, mostly by muscle ( insulin, insulin receptor). 

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... 

Glucose-6-phosphatase is another enzyme competitively inhibited by galactose-l-phosphate (15). The inhibition of hepatic glucose-6-phos-phatase is probably important in relation to hypoglycemia. 

Deficiency of hepatic glucose 6-phosphatase produces a profound fasting hypoglycemia, lactic acidosis, and hepatomegaly. Additional symptoms include ... 

Uses Type 2 DM Action Sulfonylurea T pancreatic insulin release T peripheral insulin sensitivity i hepatic glucose output Dose 100-500 mg/d w/ food, 4-hepatic impairment Caution [C, /-] CrCl <50 mL/min X in hepatic impair... 

T Pancreatic insulin release Metformin Peripheral insulin sensitivity hepatic glucose output/production i intestinal glucose absorption Dose Ist-line (naive pts), 1.25/250 mg PO daily-bid 2nd-line, 2.5/500 mg or 5/500 mg bid (max 20/2000 mg) take w/ meals, slowly T dose hold before 48 h after ionic contrast media Caution [C, -] Contra SCr >1.4 mg/dL in females or >1.5 mg/dL in males hypoxemic conditions (sepsis, recent MI) alcoholism metabolic acidosis liver Dz Disp Tabs SE HA, hypoglycemia, lactic acidosis, anorexia, N/V, rash Additional Interactions T Effects W/ amiloride, ciprofloxacin cimetidine, digoxin, miconazole, morphine, nifedipine, procainamide, quinidine, quinine, ranitidine, triamterene,... 

---