Progressive defect of insulin action on glycogen synthase in obesity and diabetes.
The purpose of the present work was to have a closer view on the changes in the regulation of glycogen synthase (GS) activity by insulin in relationship with the impairment of nonoxidative glucose disposal in human obesity. Obese patients with normal glucose tolerance (12), impaired glucose tolerance (11), diabetes (10), and lean control subjects (15) participated to the study. A euglycemic, hyperinsulinemic clamp was performed and associated with indirect calorimetry. Muscle needle biopsies were taken before and at the end of the 2-hour clamp for measurements of glycogen synthase fractional velocity and total activity. Total GS activity was significantly decreased (P <.05), while its percent activation by insulin was still normal in the obese glucose-tolerant group, and nonoxidative glucose disposal was decreased by 56% (P <.001) and glucose oxidation still normal. Total GS activity was decreased by about 50% (P <.01) and GS was unresponsive to insulin in the glucose-intolerant and diabetic groups. In conclusion, our data show that insulin-stimulated nonoxidative glucose disposal and total glycogen synthase are very early defects observed in obese patients.
Golay
Alain
A
Division of Therapeutic Education for Chronic Diseases, Department of Internal Medicine, 3HL, University Hospital, CH-1211 Geneva 14, Switzerland.
Munger
Robert
R
Assimacopoulos-Jeannet
Françoise
F
Bobbioni-Harsch
Elisabetta
E
Habicht
Frank
F
Felber
Jean-Pierre
JP
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002153:Calorimetry, Indirect; D003920:Diabetes Mellitus / Q000201:enzymology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000201:enzymology; D005951:Glucose Tolerance Test; D006006:Glycogen Synthase / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology; D009765:Obesity / Q000201:enzymology*; D010084:Oxidation-Reduction
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D006006:Glycogen Synthase