Biomaterial Database

In vivo kinetics of insulin action on peripheral glucose disposal and hepatic glucose output in normal and obese subjects. 1986

R Prager, and P Wallace, and J M Olefsky

To determine whether abnormal kinetics of insulin's biologic actions contribute to the overall insulin resistance in obesity, we compared the rate of activation and deactivation of insulin's effects to stimulate glucose disposal rate (Rd) and inhibit hepatic glucose output (HGO) in 12 nonobese and 10 obese subjects using the euglycemic clamp technique at insulin infusion rates of 15, 40, 120, and 1,200 mU/M2 per min. In both groups, stimulation of Rd was faster the higher the insulin infusion rate and the time to reach half maximal stimulation (A50 value) in normals was 52 +/- 4, 44 +/- 2, 29 +/- 3, and 21 +/- 2 min at infusion rates of 15, 40, 120, and 1,200 mU/M2 per min, respectively. In the obese subjects, the rate of activation was slower (higher A50 values) with A50 values of 74 +/- 6, P less than 0.001 (compared to normal), 64 +/- 8 min, P less than 0.001, and 28 +/- 3 min, P less than 0.01, at the 40, 120, and 1,200 mU/M2 per min insulin infusions. Deactivation of the insulin effect to stimulate glucose disposal rate (Rd) was faster in the obese group compared with normal individuals after all comparable insulin infusions. In summary: for both groups, the higher the insulin infusion rate, the higher the steady state Rd value, the faster the rate of activation and the slower the subsequent rate of deactivation. In insulin-resistant obese subjects, the rate of activation of insulin action was slower and the rate of deactivation faster at comparable insulin infusion rates. The rate of suppression of HGO was comparable in normal and obese subjects, but the rate of recovery of HGO back to basal values was faster in the obese group. And in view of the phasic manner in which insulin is normally secreted following meals, steady state insulin action is not normally achieved. Therefore, the abnormal kinetics of insulin action in insulin-resistant obese individuals may represent functionally important manifestations of the insulin resistance in this condition.

UI	MeSH Term	Description	Entries
D007263	Infusions, Parenteral	The administration of liquid medication, nutrient, or other fluid through some other route than the alimentary canal, usually over minutes or hours, either by gravity flow or often by infusion pumping.	Intra-Abdominal Infusions,Intraperitoneal Infusions,Parenteral Infusions,Peritoneal Infusions,Infusion, Intra-Abdominal,Infusion, Intraperitoneal,Infusion, Parenteral,Infusion, Peritoneal,Infusions, Intra-Abdominal,Infusions, Intraperitoneal,Infusions, Peritoneal,Intra Abdominal Infusions,Intra-Abdominal Infusion,Intraperitoneal Infusion,Parenteral Infusion,Peritoneal Infusion
D007328	Insulin	A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).	Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009765	Obesity	A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).
D001786	Blood Glucose	Glucose in blood.	Blood Sugar,Glucose, Blood,Sugar, Blood
D005934	Glucagon	A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal GLUCAGON-LIKE PEPTIDES. Glucagon is secreted by PANCREATIC ALPHA CELLS and plays an important role in regulation of BLOOD GLUCOSE concentration, ketone metabolism, and several other biochemical and physiological processes. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1511)	Glucagon (1-29),Glukagon,HG-Factor,Hyperglycemic-Glycogenolytic Factor,Proglucagon (33-61),HG Factor,Hyperglycemic Glycogenolytic Factor
D005947	Glucose	A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.	Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D005951	Glucose Tolerance Test	A test to determine the ability of an individual to maintain HOMEOSTASIS of BLOOD GLUCOSE. It includes measuring blood glucose levels in a fasting state, and at prescribed intervals before and after oral glucose intake (75 or 100 g) or intravenous infusion (0.5 g/kg).	Intravenous Glucose Tolerance,Intravenous Glucose Tolerance Test,OGTT,Oral Glucose Tolerance,Oral Glucose Tolerance Test,Glucose Tolerance Tests,Glucose Tolerance, Oral