Is hepatic glucose production increased in type 2 diabetes mellitus?

2002 ◽  
Vol 2 (3) ◽  
pp. 231-236 ◽  
Author(s):  
Henning Beck-Nielsen ◽  
Ole Hother-Nielsen ◽  
Peter Staehr
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Hepatic Glucose

scholarly journals Dopaminergic agonist bromocriptin in treatment of diabetes mellitus type 2

2011 ◽  
Vol 8 (4) ◽  
pp. 16-22
Author(s):  
O A Gerasimenko ◽  
E Pigarova ◽  
L K Dzeranova
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Animal Studies ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Postprandial Glucose ◽  
Hepatic Glucose ◽  
Treatment Of Diabetes

Bromocriptine is a sympatholytic agonist of dopamine receptors, which is now proposed for treatment of type 2 diabetes mellitus. In animal studies bromocriptine elevates the decreased levels of dopamine in hypothalamus and blocks excessive sympathetic innervations in central nervous system that results in decrease of postprandial glucose. Bromocriptine decreases hepatic glucose production and increases insulin secretion and muscle insulin sensitivity. This article reviews experimental and clinical data on the use of bromocriptine for treatment of type 2 diabetes mellitus

scholarly journals Effect of metformin on hepatic glucose production in Japanese patients with type 2 diabetes mellitus

2012 ◽  
Vol 59 (9) ◽  
pp. 845-847 ◽  
Author(s):  
Mitsuyoshi Takahara ◽  
Hideaki Kaneto ◽  
Naoto Katakami ◽  
Munehide Matsuhisa ◽  
Iichiro Shimomura
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Japanese Patients ◽  
Hepatic Glucose

scholarly journals Early-life programming of susceptibility to dysregulation of glucose metabolism and the development of Type 2 diabetes mellitus

2000 ◽  
Vol 349 (3) ◽  
pp. 657-665 ◽  
Author(s):  
Mark J. HOLNESS ◽  
Maria L. LANGDOWN ◽  
Mary C. SUGDEN
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Intolerance ◽  
Low Birthweight ◽  
Hepatic Glucose Production ◽  
Subsequent Development ◽  
Glucose Production ◽  
Glucose Disposal

There is increasing epidemiological evidence in humans which associates low birthweight with later metabolic disorders, including insulin resistance and glucose intolerance. There is evidence that nutritional and hormonal factors (e.g. maternal protein restriction, exposure to excess maternal glucocorticoids) markedly influence intra-uterine growth and development. A picture is also emerging of the biochemical and physiological mechanisms that may underlie these effects. This review focuses on recent research directed towards understanding the molecular basis of the relationship between indices of poor early growth and the subsequent development of glucose intolerance and Type 2 diabetes mellitus using animal models that attempt to recreate the process of programming via an adverse intra-uterine or neonatal environment. Emphasis is on the chain of events and potential mechanisms by which adverse adaptations affect pancreatic-β-cell insulin secretion and the sensitivity to insulin of key metabolic processes, including hepatic glucose production, skeletal-muscle glucose disposal and adipose-tissue lipolysis. Unravelling the molecular details involved in metabolic programming may provide new insights into the pathogenesis of impaired glucoregulation and Type 2 diabetes.

scholarly journals Abnormal renal and hepatic glucose metabolism in type 2 diabetes mellitus.

1998 ◽  
Vol 102 (3) ◽  
pp. 619-624 ◽  
Author(s):  
C Meyer ◽  
M Stumvoll ◽  
V Nadkarni ◽  
J Dostou ◽  
A Mitrakou ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Metabolism ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose

scholarly journals Novel liver-specific TORC2 siRNA corrects hyperglycemia in rodent models of type 2 diabetes

2009 ◽  
Vol 297 (5) ◽  
pp. E1137-E1146 ◽  
Author(s):  
Maziyar Saberi ◽  
David Bjelica ◽  
Simon Schenk ◽  
Takeshi Imamura ◽  
Gautam Bandyopadhyay ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Primary Mouse Hepatocytes ◽  
Primary Mouse ◽  
Hepatic Glucose ◽  
Zdf Rats ◽  
Mouse Hepatocytes

The transcription factor TORC2 [transducer of regulated cAMP-responsive element-binding protein (CREB) activity 2] is a major regulator of hepatic gluconeogenesis and is increased in hyperglycemic rodent models. Because chronic hyperglycemia and increased hepatic glucose production, via increased gluconeogenesis, is a key feature of type 2 diabetes, an effective in vivo method to efficiently knock down TORC2 could provide a potential therapy for treating hyperglycemia and type 2 diabetes. To assess this, primary mouse hepatocytes, high-fat diet (HFD)-fed mice, and Zucker diabetic fatty (ZDF) rats were treated with a siRNA against TORC2 (siTORC2), which was delivered via a novel lipid nanoparticle system, or control siRNA (siCON). Compared with siCON, administration of siTORC2 resulted in highly efficient, sustained (1–3 wk) knockdown of TORC2 and its gluconeogenic target genes phospho enolpyruvate carboxykinase and glucose-6-phophatase in primary mouse hepatocytes and in the livers of HFD-fed mice. In mice, this knockdown was specific to the liver and did not occur in kidney, skeletal muscle, or adipose tissue. In HFD-fed mice, siTORC2 reduced in vivo gluconeogenic capacity, fasting hepatic glucose production, and hyperglycemia, and led to improved hepatic and skeletal muscle insulin sensitivity. siTORC2 treatment also improved systemic hyperglycemia in ZDF rats. In conclusion, these results demonstrate the importance of TORC2 in modulating HGP in vivo and highlight a novel, liver-specific siRNA approach for the potential treatment of hyperglycemia and type 2 diabetes.

scholarly journals Phenotypic and Molecular Evaluation of a Chromosome 1q Region with Linkage and Association to Type 2 Diabetes in Humans

2009 ◽  
Vol 94 (4) ◽  
pp. 1401-1408 ◽  
Author(s):  
Hua Wang ◽  
Nicholas P. Hays ◽  
Swapan K. Das ◽  
Rebekah L. Craig ◽  
Winston S. Chu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Hepatic Glucose Production ◽  
Linkage Disequilibrium Block ◽  
Glucose Production ◽  
Risk Haplotype ◽  
Expression Of Genes ◽  
Hepatic Glucose

Abstract Objective: Linkage to type 2 diabetes (T2D) is well replicated on chromosome 1q21-q23. Within this region, T2D was associated with common single nucleotide polymorphisms that marked an extended linkage disequilibrium block, including the liver pyruvate kinase gene (PKLR), in several European-derived populations. In this study we sought to determine the molecular basis for the association and the phenotypic consequences of the risk haplotype. Research Design and Methods: Genes surrounding PKLR were resequenced in European-American and African-American cases and controls, and association with T2D was tested. Copy number variants (CNVs) were tested for four regions with real-time PCR. Expression of genes in the region was tested in adipose and muscle from nondiabetic subjects with each genotype. Insulin secretion, insulin sensitivity, and hepatic glucose production were tested in nondiabetic individuals with each haplotype combination. Results: No coding variant in the region was associated with T2D. CNVs were rare and not associated with T2D. PKLR was not expressed in available tissues, but expression of genes HCN3, CLK2, SCAMP3, and FDPS was not associated with haplotype combinations in adipose or muscle. Haplotype combinations were not associated with insulin secretion or peripheral insulin sensitivity, but homozygous carriers of the risk haplotype had increased hepatic glucose production during hyperinsulinemia. Conclusions: Noncoding variants in the PKLR region likely alter gene expression of one or more genes. Our extensive physiological and molecular studies suggest increased hepatic glucose production and reduced hepatic insulin sensitivity, thus pointing to PKLR itself as the most likely candidate gene in this population.

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