Obesity and type 2 diabetes impair insulin-induced suppression of glycogenolysis as well as gluconeogenesis.
To determine whether the hepatic insulin resistance of obesity and type 2 diabetes is due to impaired insulin-induced suppression of glycogenolysis as well as gluconeogenesis, 10 lean nondiabetic, 10 obese nondiabetic, and 11 obese type 2 diabetic subjects were studied after an overnight fast and during a hyperinsulinemic-euglycemic clamp. Gluconeogenesis and glycogenolysis were measured using the deuterated water method. Before the clamp, when glucose and insulin concentrations differed among the three groups, gluconeogenesis was higher in the diabetic than in the obese nondiabetic subjects (P < 0.05) and glycogenolysis was higher in the diabetic than in the lean nondiabetic subjects (P < 0.05). During the clamp, when glucose and insulin concentrations were matched and glucagon concentrations were suppressed, both glycogenolysis and gluconeogenesis were higher (P < 0.01) in the diabetic versus the obese and lean nondiabetic subjects. Furthermore, glycogenolysis and gluconeogenesis were higher (P < 0.01) in the obese than in the lean nondiabetic subjects. Plasma free fatty acid concentrations correlated (P < 0.001) with glucose production and gluconeogenesis both before and during the clamp and with glycogenolysis during the clamp (P < 0.01). We concluded that defects in the regulation of glycogenolysis as well as gluconeogenesis cause hepatic insulin resistance in obese nondiabetic and type 2 diabetic humans.
Division of Endocrinology, Metabolism, and Nutrition, Mayo Clinic, 200 1st St. SW, Rm. 5-194 Joseph, Rochester, MN 55905, USA.
Rita
R
Basu
Visvanathan
V
Chandramouli
Betty
B
Dicke
Bernard
B
Landau
Robert
R
Rizza
D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D015992:Body Mass Index; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005260:Female; D005943:Gluconeogenesis / Q000187:drug effects / Q000502:physiology*; D015309:Glucose Clamp Technique; D006003:Glycogen / Q000378:metabolism*; D006801:Humans; D006946:Hyperinsulinism; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000503:physiopathology*
D001786:Blood Glucose; D007328:Insulin; D006003:Glycogen