scholarly journals Increasing early insulin secretion compensate adequately for hepatic insulin resistance in CCl4-induced cirrhosis rats

2010 ◽  
Vol 57 (1,2) ◽  
pp. 54-61 ◽  
Author(s):  
Hidekazu Arai ◽  
Naomi Awane ◽  
Akira Mizuno ◽  
Makiko Fukaya ◽  
Masae Sakuma ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Hepatic Insulin Resistance

scholarly journals Hepatic Insulin Clearance: Mechanism and Physiology

Physiology ◽  
2019 ◽  
Vol 34 (3) ◽  
pp. 198-215 ◽  
Author(s):  
Sonia M. Najjar ◽  
Germán Perdomo
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Insulin Receptor ◽  
Hepatic Steatosis ◽  
Insulin Clearance ◽  
Hepatic Insulin Resistance ◽  
Insulin Degrading Enzyme ◽  
Insulin Receptor Tyrosine Kinase ◽  
Impaired Insulin ◽  
Hepatic Insulin Clearance

Upon its secretion from pancreatic β-cells, insulin reaches the liver through the portal circulation to exert its action and eventually undergo clearance in the hepatocytes. In addition to insulin secretion, hepatic insulin clearance regulates the homeostatic level of insulin that is required to reach peripheral insulin target tissues to elicit proper insulin action. Receptor-mediated insulin uptake followed by its degradation constitutes the basic mechanism of insulin clearance. Upon its phosphorylation by the insulin receptor tyrosine kinase, carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) takes part in the insulin-insulin receptor complex to increase the rate of its endocytosis and targeting to the degradation pathways. This review summarizes how this process is regulated and how it is associated with insulin-degrading enzyme in the liver. It also discusses the physiological implications of impaired hepatic insulin clearance: Whereas reduced insulin clearance cooperates with increased insulin secretion to compensate for insulin resistance, it can also cause hepatic insulin resistance. Because chronic hyperinsulinemia stimulates hepatic de novo lipogenesis, impaired insulin clearance also causes hepatic steatosis. Thus impaired insulin clearance can underlie the link between hepatic insulin resistance and hepatic steatosis. Delineating these regulatory pathways should lead to building more effective therapeutic strategies against metabolic syndrome.

scholarly journals Liver Enzymes Are Associated With Hepatic Insulin Resistance, Insulin Secretion, and Glucagon Concentration in Healthy Men and Women

Diabetes ◽  
2011 ◽  
Vol 60 (6) ◽  
pp. 1660-1667 ◽  
Author(s):  
F. Bonnet ◽  
P.-H. Ducluzeau ◽  
A. Gastaldelli ◽  
M. Laville ◽  
C. H. Anderwald ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Liver Enzymes ◽  
Hepatic Insulin Resistance ◽  
Men And Women ◽  
Healthy Men ◽  
Glucagon Concentration

Retinol-binding protein 4 is associated with impaired glucose tolerance but not with whole body or hepatic insulin resistance in Mexican Americans

2009 ◽  
Vol 296 (4) ◽  
pp. E758-E764 ◽  
Author(s):  
Alberto O. Chavez ◽  
Dawn K. Coletta ◽  
Subhash Kamath ◽  
Douglas T. Cromack ◽  
Adriana Monroy ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Mexican Americans ◽  
Hepatic Glucose Production ◽  
Retinol Binding Protein ◽  
Hepatic Insulin Resistance ◽  
Whole Body

Retinol-binding protein-4 (RBP4), a novel protein secreted mainly by adipose tissue, has been associated with insulin resistance in obese subjects and in individuals with type 2 diabetes mellitus (T2DM). We examined the relationship between plasma RBP4 levels, expression of RBP4 in skeletal muscle and adipose tissue, and insulin sensitivity in Mexican Americans with varying degrees of obesity and glucose tolerance. Seventy-two subjects [16 lean normal-glucose-tolerant (NGT), 17 obese NGT, and 39 subjects with impaired fasting glucose/impaired glucose tolerance/T2DM] received an oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp. Insulin secretion was measured as insulinogenic index during OGTT. In a subset of subjects, hepatic glucose production was measured by 3-[3H]glucose infusion, biopsies of the vastus lateralis muscle and subcutaneous adipose tissue were obtained under basal conditions, and quantitative RT-PCR was performed to measure the RBP4 mRNA gene expression. Plasma RBP4 was significantly elevated in impaired glucose tolerance/T2DM compared with NGT lean or obese subjects. Plasma RBP4 levels correlated with 2-h glucose, triglycerides, and hemoglobin A1c. There was no association between RBP4 levels and whole body insulin sensitivity measured with either the euglycemic insulin clamp or OGTT, basal hepatic glucose production rates, and the hepatic insulin resistance index. There was no correlation between plasma RBP4 levels and indexes of insulin secretion. RBP4 mRNA expression in skeletal muscle was similar in lean NGT subjects, obese NGT subjects, and T2DM subjects. There was no difference in RBP4 mRNA expression in adipose tissue between lean and obese NGT subjects or between NGT and T2DM individuals. Plasma RBP4 levels are elevated in T2DM and associated with impaired glucose tolerance, but not associated with obesity or insulin resistance or impaired insulin secretion in Mexican Americans.

scholarly journals Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms

2017 ◽  
Vol 114 (43) ◽  
pp. E9172-E9180 ◽  
Author(s):  
Giuseppe Ferrandino ◽  
Rachel R. Kaspari ◽  
Olga Spadaro ◽  
Andrea Reyna-Neyra ◽  
Rachel J. Perry ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Secretion ◽  
De Novo ◽  
Endogenous Glucose Production ◽  
De Novo Lipogenesis ◽  
Hepatic Insulin Resistance ◽  
Down Regulation ◽  
Lipid Utilization ◽  
Adipose Tissue Lipolysis

Hypothyroidism, a metabolic disease characterized by low thyroid hormone (TH) and high thyroid-stimulating hormone (TSH) levels in the serum, is strongly associated with nonalcoholic fatty liver disease (NAFLD). Hypothyroidism-induced NAFLD has generally been attributed to reduced TH signaling in the liver with a consequent decrease in lipid utilization. Here, we found that mildly hypothyroid mice develop NAFLD without down-regulation of hepatic TH signaling or decreased hepatic lipid utilization. NAFLD was induced by impaired suppression of adipose tissue lipolysis due to decreased insulin secretion and to a reduced response of adipose tissue itself to insulin. This condition leads to increased shuttling of fatty acids (FAs) to the liver, where they are esterified and accumulated as triglycerides. Lipid accumulation in the liver induces hepatic insulin resistance, which leads to impaired suppression of endogenous glucose production after feeding. Hepatic insulin resistance, synergistically with lowered insulin secretion, increases serum glucose levels, which stimulates de novo lipogenesis (DNL) in the liver. Up-regulation of DNL also contributes to NAFLD. In contrast, severely hypothyroid mice show down-regulation of TH signaling in their livers and profound suppression of adipose tissue lipolysis, which decreases delivery of FAs to the liver. The resulting lack of substrates for triglyceride esterification protects severely hypothyroid mice against NAFLD. Our findings demonstrate that NAFLD occurs when TH levels are mildly reduced, but, paradoxically, not when they are severely reduced. Our results show that the pathogenesis of hypothyroidism-induced NAFLD is both intra- and extrahepatic; they also reveal key metabolic differences between mild and severe hypothyroidism.

Loss of insulin secretion and hepatic insulin resistance are responsible for the development of overt diabetes in cirrhosis

1991 ◽  
Vol 13 ◽  
pp. S60
Author(s):  
A.S. Petrides ◽  
D. Schulze-Berge ◽  
D.E. Matthews ◽  
C. Vogt ◽  
G. Strohmeyer
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Hepatic Insulin Resistance ◽  
Overt Diabetes

Liver-Specific Overexpression of NOS1AP Alleviates Hepatic Insulin Resistance in Obese Mice

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1850-P
Author(s):  
CHEN WANG ◽  
KAIDA MU ◽  
TIANXUE ZHAO ◽  
HUI ZHU ◽  
WEIPING JIA
Keyword(s):  
Insulin Resistance ◽  
Hepatic Insulin Resistance ◽  
Obese Mice

1516-P: A Comparison of the Contributions of Impaired Insulin Secretion and Insulin Resistance to the Development of Type 2 Diabetes in a Japanese Community: The Hisayama Study

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1516-P
Author(s):  
MASAHITO YOSHINARI ◽  
YOICHIRO HIRAKAWA ◽  
JUN HATA ◽  
MAYU HIGASHIOKA ◽  
TAKANORI HONDA ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Impaired Insulin Secretion ◽  
Impaired Insulin
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