Comparison of the effects of acute changes in the circulating plasma glucose concentration on rates of glucose production (GP) in non-diabetic and diabetic individuals. Increase hepatic glucose production is the major cause of postabsorptive hyperglycemia (high blood sugar) in diabetes mellitis. Insulin maintains glucose homeostasis (stability in normal body states) by its principal actions of stimulation of glucose uptake in skeletal muscle and supression of GP. The study aim is to determine whether and how hyperglycemia alters hepatic glucose fluxes in non-diabetic and DM (diabetes mellitis) individuals in the presence of 'pancreatic clamp' conditions. Rates of GP and glucose cycling will be measured during somatostatin infusion and basal hormone replacement in the presence of normoglycemia and in response to standard increases in plasma glucose concentration. The potential role of hepatic glucokinase (a catalytic enzyme specific for glucose) in glucose induced inhibition of GP. There will be three study groups of 14 subjects, two with diabetes mellitis and one with normal glucose tolerance, matched for age, sex, body mass to the DM groups. All subjects will be 35-70 years old, in otherwise good health, not participating in any other study. Screening will include history, physical examination, hematologic, lipid, and chemistry, and consent procedures. Medications will be discontinued several hours prior to the study. All participants will be consuming a weight-maintaining diet containing at least 250 grams of carbohydrates per day for several days before the study. DM patients will be admitted and insulin will be infused by vein and continued overnight. Control patients will be admitted on the day of the study for an overnight fast. Both control and DM patients will be studied after fasting. Two tubes will be inserted, one for infusion, the other for blood sampling. During the study, several infusions of insulin and fructose and blood tests will be done. Indirect calorimetry will be done.
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