The lack of functional nicotinamide nucleotide transhydrogenase only moderately contributes to the impairment of glucose tolerance and glucose-stimulated insulin secretion in C57BL/6J vs C57BL/6N mice

Diabetologia ◽  
2021 ◽  
Vol 64 (11) ◽  
pp. 2550-2561
Author(s):  
Anne-Françoise Close ◽  
Heeyoung Chae ◽  
Jean-Christophe Jonas
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Nicotinamide Nucleotide Transhydrogenase ◽  
Glucose Stimulated Insulin Secretion

scholarly journals Acid Hydrolyzed Silk Peptide Consumption Improves Anti-Diabetic Symptoms by Potentiating Insulin Secretion and Preventing Gut Microbiome Dysbiosis in Non-Obese Type 2 Diabetic Animals

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 311 ◽  
Author(s):  
Sunmin Park ◽  
Ting Zhang ◽  
Jing Yi Qiu ◽  
Xuangao Wu ◽  
Jeong-Yong Lee ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Normal Control ◽  
Positive Control ◽  
Control Group ◽  
Sensitivity Testing ◽  
Insulin Tolerance ◽  
Glucose Stimulated Insulin Secretion

Silk fibroin hydrolysates have been reported to reduce hyperglycemia, but the mechanism has not been determined in Asian type 2 diabetes (T2DM). We hypothesized that the consumption of acid hydrolyzed silk peptides (SPs) alleviates hyperglycemia by improving insulin sensitivity and subsequently normalizing glucose-stimulated insulin secretion in T2DM. We investigated this hypothesis in a partial pancreatectomized (Px) rat model. Px rats was assigned randomly to the following six groups and fed assigned diet for 8 weeks: the Px-control (0.5 g/kg/day dextrin), the SP-L (0.05 g/kg/day), the SP-M (0.1 g/kg/day), the SP-H (0.5 g/kg/day), the positive-control (40 mg/kg/day metformin), or the normal-control (sham-operated rats; 0.5 g/kg/day dextrin). SPs contained high levels of glycine, alanine, and serine. We found SPs dose-dependently increased food efficiency and body weight gain in Px rats. Animals in the Px-control group rats exhibited lower glucose metabolism, as evidenced by impaired glucose-stimulated insulin secretion coupled with impaired insulin sensitivity, and reduced bone mineral density (BMD) and lean body mass (LBM), compared to the normal-control. SPs and metformin similarly partially protected against Px-induced BMD loss in the lumbar spine and femur. Px-induced decreases in LBM were dose-dependently prevented by SPs, and muscle forces in the SP-M and SP-H groups were maintained at the normal-control level. Glucose tolerance was dose-dependently improved by SPs as determined by oral glucose tolerance and oral maltose tolerance tests, and glucose tolerances were similar in the SP-H and positive-control groups. Insulin tolerance, an index of insulin sensitivity, was dose-dependently enhanced by SPs, and the SP-H group exhibited better insulin tolerance than the positive-control group as determined by intraperitoneal insulin sensitivity testing. Insulin secretory capacity assessed using a hyperglycemic clamp improved in the following order: Px-control <SA-L <SA-M <positive-control <SA-H <normal-control. SP-M prevented gut microbiota dysbiosis. In conclusion, SPs administered at 0.1–0.5 g/kg/day improved glucose regulation by potentiating both insulin secretion and insulin sensitivity in non-obese T2DM rats.

scholarly journals Improved glucose tolerance with DPPIV inhibition requires β‐cell SENP1 amplification of glucose‐stimulated insulin secretion

2020 ◽  
Vol 8 (8) ◽  
Author(s):  
Mourad Ferdaoussi ◽  
Nancy Smith ◽  
Haopeng Lin ◽  
Austin Bautista ◽  
Aliya F. Spigelman ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Β Cell ◽  
Glucose Stimulated Insulin Secretion

scholarly journals Effects of birth weight, sex and neonatal glucocorticoid overexposure on glucose–insulin dynamics in young adult horses

2016 ◽  
Vol 8 (2) ◽  
pp. 206-215 ◽  
Author(s):  
O. A. Valenzuela ◽  
J. K. Jellyman ◽  
V. L. Allen ◽  
N. B. Holdstock ◽  
A. J. Forhead ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Birth Weight ◽  
Insulin Sensitivity ◽  
Young Adult ◽  
Glucose Tolerance ◽  
Metabolic Phenotype ◽  
Whole Body ◽  
Sexually Dimorphic ◽  
Genetic And Environmental Factors ◽  
Glucose Stimulated Insulin Secretion

In several species, adult metabolic phenotype is influenced by the intrauterine environment, often in a sex-linked manner. In horses, there is also a window of susceptibility to programming immediately after birth but whether adult glucose–insulin dynamics are altered by neonatal conditions remains unknown. Thus, this study investigated the effects of birth weight, sex and neonatal glucocorticoid overexposure on glucose–insulin dynamics of young adult horses. For the first 5 days after birth, term foals were treated with saline as a control or ACTH to raise cortisol levels to those of stressed neonates. At 1 and 2 years of age, insulin secretion and sensitivity were measured by exogenous glucose administration and hyperinsulinaemic–euglycaemic clamp, respectively. Glucose-stimulated insulin secretion was less in males than females at both ages, although there were no sex-linked differences in glucose tolerance. Insulin sensitivity was greater in females than males at 1 year but not 2 years of age. Birth weight was inversely related to the area under the glucose curve and positively correlated to insulin sensitivity at 2 years but not 1 year of age. In contrast, neonatal glucocorticoid overexposure induced by adrenocorticotropic hormone (ACTH) treatment had no effect on whole body glucose tolerance, insulin secretion or insulin sensitivity at either age, although this treatment altered insulin receptor abundance in specific skeletal muscles of the 2-year-old horses. These findings show that glucose–insulin dynamics in young adult horses are sexually dimorphic and determined by a combination of genetic and environmental factors acting during early life.

scholarly journals The Deletion Variant of Nicotinamide Nucleotide Transhydrogenase (Nnt) Does Not Affect Insulin Secretion or Glucose Tolerance

Endocrinology ◽  
2010 ◽  
Vol 151 (1) ◽  
pp. 96-102 ◽  
Author(s):  
Nicole Wong ◽  
Amy R. Blair ◽  
Grant Morahan ◽  
Sofianos Andrikopoulos
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
Oral Glucose ◽  
Diabetes Research ◽  
Activity Levels ◽  
Inner Mitochondrial Membrane ◽  
Nicotinamide Nucleotide Transhydrogenase ◽  
Expression And Activity

Abstract The C57BL/6J (B6J) strain is the most widely used mouse strain in metabolic research. B6J mice produce a truncated form of nicotinamide nucleotide transhydrogenase (NNT), an enzyme that pumps protons across the inner mitochondrial membrane. It has been proposed that this results in B6J mice having reduced insulin secretion and glucose intolerance compared with other strains of mice (e.g. C3H/HeH and DBA/2) that have a full-length NNT. The aim of this study was to determine whether truncated NNT was associated with reduced insulin secretion and glucose intolerance, comparing B6 substrains that differ in having a truncated NNT. C57BL/6N (B6N) mice have wild-type Nnt. We compared Nnt expression and activity levels as well as in vivo insulin secretion and glucose tolerance between these mice and B6J. Body weights and specific fat-pad depot masses were alike and Nnt expression and activity levels were similar between B6N and B6J mice. Glucose-mediated insulin secretion and insulin sensitivity were comparable between the two groups of mice, as were plasma glucose and insulin levels during the oral glucose tolerance test. The presence of a truncated Nnt did not affect insulin secretion or glucose tolerance on the C57BL/6 background. We suggest that low or normal levels of NNT (regardless of truncation) have little effect on insulin secretion. Rather, it is the increase in expression of Nnt that regulates and enhances insulin secretion. Our data confirm that B6J is a reasonable control strain for diabetes research; this is especially important considering that it is the strain commonly used to generate genetically modified animals.

scholarly journals Peroxiredoxin 6 Is a Key Antioxidant Enzyme in Modulating the Link between Glycemic and Lipogenic Metabolism

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Roberto Arriga ◽  
Francesca Pacifici ◽  
Barbara Capuani ◽  
Andrea Coppola ◽  
Augusto Orlandi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Serum Levels ◽  
Protective Role ◽  
Peroxiredoxin 6 ◽  
Food And Drink ◽  
Glucose Stimulated Insulin Secretion ◽  
Mice Liver

Insulin action and often glucose-stimulated insulin secretion are reduced in obesity. In addition, the excessive intake of lipids increases oxidative stress leading to overt type 2 diabetes mellitus (T2DM). Among the antioxidative defense systems, peroxiredoxin 6 (PRDX6) is able to reduce H2O2 and short chain and phospholipid hydroperoxides. Increasing evidences suggest that PRDX6 is involved in the pathogenesis of atherosclerosis and T2DM, but its role in the etiopathology of obesity and its complications is still not known. Therefore, in the present study, we sought to investigate this association by using PRDX6 knockout mice (PRDX6-/-). Metabolic parameters, like carbon dioxide (VCO2) production, oxygen consumption (VO2), and the respiratory exchange ratio (RER), were determined using metabolic cages. Intraperitoneal insulin and glucose tolerance tests were performed to evaluate insulin sensitivity and glucose tolerance, respectively. Liver and pancreas histochemical analyses were also evaluated. The expression of enzymes involved in lipid and glucose metabolism was analyzed by real-time PCR. Following 24 weeks of high-fat-diet (HFD), PRDX6-/- mice showed weight gain and higher food and drink intake compared to controls. VO2 consumption and VCO2 production decreased in PRDX6-/- mice, while the RER was lower than 0.7 indicating a prevalent lipid metabolism. PRDX6-/- mice fed with HFD showed a further deterioration on insulin sensitivity and glucose-stimulated insulin secretion. Furthermore, in PRDX6-/- mice, insulin did not suppress adipose tissue lipolysis with consequent hepatic lipid overload and higher serum levels of ALT, cholesterol, and triglycerides. Interestingly, in PRDX6-/- mice, liver and adipose tissue were associated with proinflammatory gene upregulation. Finally, PRDX6-/- mice showed a higher rate of nonalcoholic steatohepatitis (NASH) compared to control. Our results suggest that PRDX6 may have a functional and protective role in the development of obesity-related metabolic disorders such as liver diseases and T2DM and may be considered a potential therapeutic target against these illnesses.

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