Effects of Type 2 Diabetes on the Regulation of Hepatic Glucose Metabolism

Glucose production is inappropriately increased in people with type 2 diabetes both before and after food ingestion. Excessive postprandial glucose production occurs in the presence of decreased and delayed insulin secretion and lack of suppression of glucagon release. These abnormalities in hormone secretion, coupled with impaired insulin-induced suppression of glucose production and stimulation of splanchnic glucose uptake, likely account in large part for the excessive amounts of glucose that reach the systemic circulation for disposal by peripheral tissues following food ingestion. In contrast, when adequate basal insulin concentrations are present, neither glucagon-induced stimulation of glucose production nor glucose-induced suppression of glucose production differs in diabetic and nondiabetic subjects matched for gender, age, and degree of obesity. However, when insulin secretion is defective, lack of suppression of glucagon can cause substantial hyperglycemia by enhancing rates of glucose production. Therefore, normalization of hepatic glucose metabolism in people with type 2 diabetes mellitus likely will require normalization of insulin and glucagon secretion as well as hepatic insulin action.

[1]  G. Mithieux,et al.  Induction of control genes in intestinal gluconeogenesis is sequential during fasting and maximal in diabetes. , 2004, American journal of physiology. Endocrinology and metabolism.

[2]  J. Holst,et al.  Does overnight normalization of plasma glucose by insulin infusion affect assessment of glucose metabolism in Type 2 diabetes? , 2003, Diabetic medicine : a journal of the British Diabetic Association.

[3]  J. Radziuk,et al.  Quantitation of basal endogenous glucose production in Type II diabetes: importance of the volume of distribution , 2002, Diabetologia.

[4]  I. Gabriely,et al.  Glycemic control determines hepatic and peripheral glucose effectiveness in type 2 diabetic subjects. , 2002, Diabetes.

[5]  M. Jensen,et al.  Type 2 diabetes impairs splanchnic uptake of glucose but does not alter intestinal glucose absorption during enteral glucose feeding: additional evidence for a defect in hepatic glucokinase activity. , 2001, Diabetes.

[6]  M. Jensen,et al.  Effects of type 2 diabetes on the ability of insulin and glucose to regulate splanchnic and muscle glucose metabolism: evidence for a defect in hepatic glucokinase activity. , 2000, Diabetes.

[7]  C Cobelli,et al.  Normal glucose-induced suppression of glucose production but impaired stimulation of glucose disposal in type 2 diabetes: evidence for a concentration-dependent defect in uptake. , 1998, Diabetes.

[8]  R. Rizza,et al.  Assessment of Hepatic Sensitivity to Glucagon in NIDDM: Use as a Tool to Estimate the Contribution of the Indirect Pathway to Nocturnal Glycogen Synthesis , 1997, Diabetes.

[9]  C Cobelli,et al.  Impaired Basal Glucose Effectiveness in NIDDM: Contribution of Defects in Glucose Disappearance and Production, Measured Using an Optimized Minimal Model Independent Protocol , 1997, Diabetes.

[10]  R. Rizza,et al.  Contribution to Postprandial Hyperglycemia and Effect on Initial Splanchnic Glucose Clearance of Hepatic Glucose Cycling in Glucose-Intolerant or NIDDM Patients , 1991, Diabetes.

[11]  R. Rizza,et al.  Hepatic and Extrahepatic Responses to Insulin in NIDDM and Nondiabetic Humans: Assessment in Absence of Artifact Introduced by Tritiated Nonglucose Contaminants , 1990, Diabetes.

[12]  R. Bergman,et al.  Assessment of insulin sensitivity in vivo: a critical review. , 1989, Diabetes/metabolism reviews.

[13]  R. Bergman,et al.  Modeling Error and Apparent Isotope Discrimination Confound Estimation of Endogenous Glucose Production During Euglycemic Glucose Clamps , 1988, Diabetes.

[14]  R. Rizza,et al.  Effects of Tolazamide and Exogenous Insulin on Pattern of Postprandial Carbohydrate Metabolism in Patients With Non-Insulin-Dependent Diabetes Mellitus: Results of Randomized Crossover Trial , 1987, Diabetes.

[15]  R N Bergman,et al.  Estimation of Endogenous Glucose Production During Hyperinsulinemic-Euglycemic Glucose Clamps: Comparison of Unlabeled and Labeled Exogenous Glucose Infusates , 1987, Diabetes.

[16]  R. Wolfe,et al.  The realiability of rates of glucose appearance in vivo calculated from constant tracer infusions. , 1978, The Biochemical journal.

[17]  R. Steele,et al.  Measurement of size and turnover rate of body glucose pool by the isotope dilution method. , 1956, The American journal of physiology.