Obesity and type 2 diabetes impair insulin-induced suppression of glycogenolysis as well as gluconeogenesis

Rita Basu, Visvanathan Chandramouli, Betty Dicke, Bernard Landau, Robert Rizza

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1942-1948
Number of pages7
JournalDiabetes
Volume54
Issue number7
DOIs
StatePublished - Jul 2005

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Glycogenolysis
Gluconeogenesis
Type 2 Diabetes Mellitus
Obesity
Insulin
Glucose Clamp Technique
Insulin Resistance
Glucose
Liver
Glucagon
Nonesterified Fatty Acids
Water

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

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Obesity and type 2 diabetes impair insulin-induced suppression of glycogenolysis as well as gluconeogenesis. / Basu, Rita; Chandramouli, Visvanathan; Dicke, Betty; Landau, Bernard; Rizza, Robert.

In: Diabetes, Vol. 54, No. 7, 07.2005, p. 1942-1948.

Research output: Contribution to journalArticle

Basu, Rita ; Chandramouli, Visvanathan ; Dicke, Betty ; Landau, Bernard ; Rizza, Robert. / Obesity and type 2 diabetes impair insulin-induced suppression of glycogenolysis as well as gluconeogenesis. In: Diabetes. 2005 ; Vol. 54, No. 7. pp. 1942-1948.
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