Pancreatic Insulin Secretion in Rats Fed a Soy Protein High Fat Diet Depends on the Interaction between the Amino Acid Pattern and Isoflavones

The aim of this study was to investigate the effect of subdiaphragmatic vagotomy on insulin sensitivity, secretion, and degradation in metabolic programmed mice, induced by a low-protein diet early in life, followed by exposure to a high-fat diet in adulthood. Weaned 30-day-old C57Bl/6 mice were submitted to a low-protein diet (6% protein). After 4 weeks, the mice were distributed into three groups: LP group, which continued receiving a low-protein diet; LP + HF group, which started to receive a high-fat diet; and LP + HFvag group, which underwent vagotomy and also was kept at a high-fat diet. Glucose-stimulated insulin secretion (GSIS) in isolated islets, ipGTT, ipITT, in vivo insulin clearance, and liver expression of the insulin-degrading enzyme (IDE) was accessed. Vagotomy improved glucose tolerance and reduced insulin secretion but did not alter adiposity and insulin sensitivity in the LP + HFvag, compared with the LP + HF group. Improvement in glucose tolerance was accompanied by increased insulinemia, probably due to a diminished insulin clearance, as judged by the lower C-peptide : insulin ratio, during the ipGTT. Finally, vagotomy also reduced liver IDE expression in this group. In conclusion, when submitted to vagotomy, the metabolic programmed mice showed improved glucose tolerance, associated with an increase of plasma insulin concentration as a result of insulin clearance reduction, a phenomenon probably due to diminished liver IDE expression.

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IP6-assisted CSN-COP1 competition regulates a CRL4-ETV5 proteolytic checkpoint to safeguard glucose-induced insulin secretion

Nature Communications ◽

10.1038/s41467-021-22941-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Hong Lin ◽

Yuan Yan ◽

Yifan Luo ◽

Wing Yan So ◽

Xiayun Wei ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Secretion ◽

High Fat Diet ◽

E3 Ligase ◽

Human Islets ◽

Cop9 Signalosome ◽

Congenital Hyperinsulinism ◽

High Fat ◽

Transcriptional Suppressor

AbstractCOP1 and COP9 signalosome (CSN) are the substrate receptor and deneddylase of CRL4 E3 ligase, respectively. How they functionally interact remains unclear. Here, we uncover COP1–CSN antagonism during glucose-induced insulin secretion. Heterozygous Csn2WT/K70E mice with partially disrupted binding of IP6, a CSN cofactor, display congenital hyperinsulinism and insulin resistance. This is due to increased Cul4 neddylation, CRL4COP1 E3 assembly, and ubiquitylation of ETV5, an obesity-associated transcriptional suppressor of insulin secretion. Hyperglycemia reciprocally regulates CRL4-CSN versus CRL4COP1 assembly to promote ETV5 degradation. Excessive ETV5 degradation is a hallmark of Csn2WT/K70E, high-fat diet-treated, and ob/ob mice. The CRL neddylation inhibitor Pevonedistat/MLN4924 stabilizes ETV5 and remediates the hyperinsulinemia and obesity/diabetes phenotypes of these mice. These observations were extended to human islets and EndoC-βH1 cells. Thus, a CRL4COP1-ETV5 proteolytic checkpoint licensing GSIS is safeguarded by IP6-assisted CSN-COP1 competition. Deregulation of the IP6-CSN-CRL4COP1-ETV5 axis underlies hyperinsulinemia and can be intervened to reduce obesity and diabetic risk.

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Micro-RNA 206 affects glucose induced insulin secretion under high-fat diet

Atherosclerosis ◽

10.1016/j.atherosclerosis.2015.04.292 ◽

2015 ◽

Vol 241 (1) ◽

pp. e83

Author(s):

M. Vinod ◽

J.V. Patankar ◽

V. Sachdev ◽

W.A.E.L. Al-Zoughbi ◽

G. Höfler ◽

...

Keyword(s):

Insulin Secretion ◽

High Fat Diet ◽

Micro Rna ◽

High Fat

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Soy protein intake prevents adipocyte hypertrophy in rats fed a high fat diet

The FASEB Journal ◽

10.1096/fasebj.20.4.a595-c ◽

2006 ◽

Vol 20 (4) ◽

Author(s):

Ivan Torre‐Villalvazo ◽

Armando R Tovar ◽

Nimbe Torres

Keyword(s):

Soy Protein ◽

High Fat Diet ◽

Protein Intake ◽

High Fat ◽

Adipocyte Hypertrophy

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Dietary Soy Protein Reduces Cardiac Lipid Accumulation and the Ceramide Concentration in High-Fat Diet-Fed Rats and ob/ob Mice

Journal of Nutrition ◽

10.3945/jn.109.109769 ◽

2009 ◽

Vol 139 (12) ◽

pp. 2237-2243 ◽

Cited By ~ 21

Author(s):

Ivan Torre-Villalvazo ◽

Fabiola Gonzalez ◽

Carlos A. Aguilar-Salinas ◽

Armando R. Tovar ◽

Nimbe Torres

Keyword(s):

Soy Protein ◽

Lipid Accumulation ◽

High Fat Diet ◽

High Fat ◽

Cardiac Lipid

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High fat diet incorporated with meat proteins changes biomarkers of lipid metabolism, antioxidant activities, and the serum metabolomic profile in Glrx1−/− mice

Food & Function ◽

10.1039/c9fo02207d ◽

2020 ◽

Vol 11 (1) ◽

pp. 236-252 ◽

Cited By ~ 4

Author(s):

Muhammad Ijaz Ahmad ◽

Muhammad Umair Ijaz ◽

Muzahir Hussain ◽

Iftikhar Ali Khan ◽

Noreen Mehmood ◽

...

Keyword(s):

Lipid Metabolism ◽

Linoleic Acid ◽

Bile Acid ◽

Amino Acid ◽

High Fat Diet ◽

Antioxidant Activities ◽

Glutathione Metabolism ◽

Metabolomic Profile ◽

High Fat ◽

Meat Proteins

High-fat mutton protein diet may alter lipid-, linoleic acid-, amino acid-, bile acid-, sphingolipid-, glycine-, serine- and glutathione-metabolism pathways in Glrx−/− mice whereas HFF diet ameliorated NAFLD by modifying these pathways.

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Reduced Serum Cholesterol and Triglyceride Levels in a Choline-Deficient L-Amino Acid-Defined High-Fat Diet (CDAHFD)-Induced Mouse Model of Non-alcoholic Steatohepatitis (NASH)

Biological and Pharmaceutical Bulletin ◽

10.1248/bpb.b19-00338 ◽

2020 ◽

Vol 43 (4) ◽

pp. 616-618 ◽

Cited By ~ 1

Author(s):

Daisuke Yasuda ◽

Haruki Torii ◽

Rumiko Shimizu ◽

Yoshinori Hiraoka ◽

Noriaki Kume

Keyword(s):

Amino Acid ◽

Mouse Model ◽

Serum Cholesterol ◽

High Fat Diet ◽

High Fat ◽

Alcoholic Steatohepatitis

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Effects of Caffeine and Chlorogenic Acid on Nonalcoholic Steatohepatitis in Mice Induced by Choline-Deficient, L-Amino Acid-Defined, High-Fat Diet

Nutrients ◽

10.3390/nu12123886 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3886

Author(s):

Erdenetsogt Dungubat ◽

Shiori Watabe ◽

Arisa Togashi-Kumagai ◽

Masato Watanabe ◽

Yasuyuki Kobayashi ◽

...

Keyword(s):

Amino Acid ◽

Chlorogenic Acid ◽

Nonalcoholic Steatohepatitis ◽

High Fat Diet ◽

Cell Injury ◽

Control Diet ◽

Experimental Studies ◽

High Fat ◽

Nonalcoholic Fatty Liver ◽

Hepatic Expression

Several recent experimental studies have investigated the effects of caffeine and chlorogenic acid (CGA), representative ingredients of coffee, on nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). However, the results are conflicting, and their effects are yet to be clarified. In the present study, we examined the effects of caffeine and CGA on choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-fed mice, relatively new model mice of NASH. Seven-week-old male C57BL/6J mice were divided into the following groups: Control diet (control), CDAHFD (CDAHFD), CDAHFD supplemented with 0.05% (w/w) caffeine (caffeine), and CDAHFD supplemented with 0.1% (w/w) CGA (CGA). After seven weeks, the mice were killed and serum biochemical, histopathological, and molecular analyses were performed. Serum alanine aminotransferase (ALT) levels were significantly higher in the caffeine and CGA groups than in the CDAHFD group. On image analysis, the prevalence of Oil red O-positive areas (reflecting steatosis) was significantly higher in the caffeine group than in the CDAHFD group, and that of CD45R-positive areas (reflecting lymphocytic infiltration) in the hepatic lobule was significantly higher in the caffeine and CGA groups than in the CDAHFD group. Hepatic expression of interleukin (IL)-6 mRNA was higher in the caffeine and CGA groups than in the CDAHFD group, and the difference was statistically significant for the caffeine group. In conclusion, in the present study, caffeine and CGA significantly worsened the markers of liver cell injury, inflammation, and/or steatosis in NASH lesions in mice.

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