Insulin Glucose output

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). 

This situation arises mainly when the blood level of insulin is high - abnormally high for the given condition. Insulin not only stimulates peripheral utilisation but also inhibits glucose output by the liver so that hypoglycaemia can develop rapidly. Four examples are given. 

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,... 

Mechanism of Action An antidiabetic that improves target-cell response to insulin without increasing pancreatic insulin secretion. Decreases hepatic glucose output and increases insulin-dependent glucose utilization in skeletal muscle. Therapeutic Effect Lowers blood glucose concentration. 

Mechanism of Action Potent and highly selective agonist for peroxisome proliferator-activated receptor-gamma (PPAR(gamma)) which decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. 

Another main change is in the insulin sensitivity at different tissues. For example, the effect of insulin on glucose uptake is decreased. Insulin has the same inhibitory effect on lipolysis and on hepatic glucose output, and inside the cells the removal of glucose-6-phosphate is decreased. The different changes in the metabolic traffic result in a spectrum of possible patient variants. Common for them all is an increased plasma glucose concentration and increased meal-related variations. 

Current marketed antidiabetic treatments are shown in Table 3. These dmgs may act to improve insulin sensitivity, decrease hepatic glucose output, decrease the absorption of glucose in the GI tract, or stimulate the secretion of insulin. Numerous studies... 

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