Regulation of Glucose Production in the Pathogenesis of Type 2 Diabetes

被引:27
作者
Sargsyan, Ashot [1 ]
Herman, Mark A. [1 ,2 ]
机构
[1] Duke Univ, Duke Mol Physiol Inst, Durham, NC 27708 USA
[2] Duke Univ, Div Diabet Endocrinol & Metab, Durham, NC 27708 USA
关键词
Glucose production; Diabetes; Gluconeogenesis; Glycogenolysis; Glucose; 6; phosphate; ChREBP; HEPATIC INSULIN-RESISTANCE; TRANSCRIPTION FACTOR FOXO1; FREE FATTY-ACIDS; GLYCOGEN-SYNTHESIS; PROTEIN-KINASE; FASTING HYPERGLYCEMIA; SIGNALING PATHWAYS; PERIPHERAL GLUCOSE; GENE-EXPRESSION; ADIPOSE-TISSUE;
D O I
10.1007/s11892-019-1195-5
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Purpose of Review Increased glucose production associated with hepatic insulin resistance contributes to the development of hyperglycemia in T2D. The molecular mechanisms accounting for increased glucose production remain controversial. Our aims were to review recent literature concerning molecular mechanisms regulating glucose production and to discuss these mechanisms in the context of physiological experiments and observations in humans and large animal models. Recent Findings Genetic intervention studies in rodents demonstrate that insulin can control hepatic glucose production through both direct effects on the liver, and through indirect effects to inhibit adipose tissue lipolysis and limit gluconeogenic substrate delivery. However, recent experiments in canine models indicate that the direct effects of insulin on the liver are dominant over the indirect effects to regulate glucose production. Recent molecular studies have also identified insulin-independent mechanisms by which hepatocytes sense intrahepatic carbohydrate levels to regulate carbohydrate disposal. Dysregulation of hepatic carbohydrate sensing systems may participate in increased glucose production in the development of diabetes.
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页数:11
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