Chromium Picolinate Supplementation Attenuates Body Weight Gain and Increases Insulin Sensitivity in Subjects With Type 2 Diabetes: Response to Mark

We report the discovery of a novel glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor dual agonist that shows balanced agonism towards both the incretin receptor. The dual agonism of GLP-1 and GIP receptor was achieved by replacing the tryptophan cage of exendin-4 with the C- terminal undecapeptide sequence of oxyntomodulin along with a single amino acid substitution from histidine to tyrosine at the amino terminus of the peptide. The structural modification places lysine 30 of the novel incretin agonist in frame with the corresponding lysine residue in the native GIP sequence. The novel incretin agonist, named I-M-150847, promotes robust glucose-stimulated insulin exocytosis in cultured pancreatic beta cells. Chronic administration of I-M-150847 to mice fed on the high-fat diet improves glucose tolerance, decreases food intake, decreases visceral adiposity and body weight gain demonstrating its therapeutic potential in ameliorating type 2 Diabetes and Obesity.

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Social Isolation Affects the Development of Obesity and Type 2 Diabetes in Mice

Endocrinology ◽

10.1210/en.2007-0296 ◽

2007 ◽

Vol 148 (10) ◽

pp. 4658-4666 ◽

Cited By ~ 53

Author(s):

Katsunori Nonogaki ◽

Kana Nozue ◽

Yoshitomo Oka

Keyword(s):

Type 2 Diabetes ◽

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Social Isolation ◽

Food Consumption ◽

Leptin Receptor ◽

Body Weight Gain ◽

Kkay Mice

Social isolation is associated with increased risks of mortality and morbidity. In this study, we show that chronic individual housing accelerated body weight gain and adiposity in KK mice but not C57BL6J mice, and fully developed diabetes in KKAy mice. Individually housed KK and KKAy mice increased body weight gain over the initial 2 wk without increased daily average food consumption compared with group-housed animals. The individually housed KK and KKAy mice then gradually increased food consumption for the next 1 wk. The chronic social isolation-induced obesity (SIO) was associated with hyperleptinemia and lower plasma corticosterone and active ghrelin levels but not hyperinsulinemia. Elevated plasma leptin in the SIO suppressed expression of 5-HT2C receptor in white adipose tissue. The SIO was also associated with decreased expression of β3-adrenergic receptors in white adipose tissue and hypothalamic leptin receptor, which might be secondary to the enhanced adiposity. Interestingly, social isolation acutely reduced food consumption and body weight gain compared with group-housed obese db/db mice with leptin receptor deficiency. Social isolation-induced hyperglycemia in KKAy mice was associated with increased expression of hepatic gluconeogenetic genes independent of insulin. These findings suggest that social isolation promotes obesity due to primary decreased energy expenditure and secondary increased food consumption, which are independent of the disturbed leptin signaling, in KK mice, and develops into insulin-independent diabetes associated with increased expression of hepatic gluconeogenetic genes in KKAy mice. Thus, social isolation can be included in the environmental factors that contribute to the development of obesity and type 2 diabetes.

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Association between variability in body mass index and development of type 2 diabetes: Panasonic cohort study

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2021-002123 ◽

2021 ◽

Vol 9 (1) ◽

pp. e002123

Author(s):

Hiroshi Okada ◽

Masahide Hamaguchi ◽

Momoko Habu ◽

Kazushiro Kurogi ◽

Hiroaki Murata ◽

...

Keyword(s):

Type 2 Diabetes ◽

Body Mass Index ◽

Body Weight ◽

Weight Gain ◽

Body Mass ◽

Cox Regression ◽

Body Weight Gain ◽

Design And Methods ◽

Fourth Quartile

IntroductionContrasting results have been reported for the association between the variability in body weight and development of diabetes. In the present study, we evaluated the association between the variability in body mass index (BMI) and development of type 2 diabetes in 19 412 Japanese participants without obesity and without body weight gain or loss during the study period.Research design and methodsWe recorded body weight of the participants consecutively each year in Panasonic Corporation, Osaka, Japan from 2008 to 2014 to evaluate the variability of BMI. The participants with obesity (BMI ≥25 kg/m2) at baseline and body weight gain or loss from 2008 to 2014 (delta BMI ≥±1 kg/m2) were excluded from the study. In total, 416 participants developed type 2 diabetes from 2015 to 2018. We used coefficient of variation (CV) to represent the variability in BMI during 6 years of the study period.ResultsCox regression analyses revealed that the risk of developing type 2 diabetes was higher in the fourth quartile (HR 1.33; 95% CI 1.01 to 1.75) of CV of BMI than that in the first quartile (lowest quartile) of CV of BMI after adjusting for multiple confounding factors. The risk for developing diabetes increased by 11.1% per 1% increase in CV of BMI.ConclusionsIn conclusion, the variability in BMI is a risk factor for the development of diabetes in the Japanese population without obesity and without body weight gain or loss.

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Quantitative relationship between body weight gain in adulthood and incident type 2 diabetes: a meta-analysis

Obesity Reviews ◽

10.1111/obr.12129 ◽

2013 ◽

Vol 15 (3) ◽

pp. 202-214 ◽

Cited By ~ 55

Author(s):

S. Kodama ◽

C. Horikawa ◽

K. Fujihara ◽

S. Yoshizawa ◽

Y. Yachi ◽

...

Keyword(s):

Type 2 Diabetes ◽

Body Weight ◽

Weight Gain ◽

Body Weight Gain ◽

Meta Analysis ◽

Quantitative Relationship ◽

Incident Type ◽

Incident Type 2 Diabetes

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Small-Molecule Insulin Mimetic Reduces Hyperglycemia and Obesity in a Nongenetic Mouse Model of Type 2 Diabetes

Endocrinology ◽

10.1210/en.2004-0610 ◽

2004 ◽

Vol 145 (11) ◽

pp. 5259-5268 ◽

Cited By ~ 16

Author(s):

Mathias Z. Strowski ◽

Zhihua Li ◽

Deborah Szalkowski ◽

Xiaolan Shen ◽

Xiao-Ming Guan ◽

...

Keyword(s):

Type 2 Diabetes ◽

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Mouse Model ◽

Small Molecule ◽

White Adipose Tissue ◽

Body Weight Gain ◽

Nonesterified Fatty Acids

Abstract Adiposity positively correlates with insulin resistance and is a major risk factor of type 2 diabetes. Administration of exogenous insulin, which acts as an anabolic factor, facilitates adipogenesis. Recently nonpeptidal insulin receptor (IR) activators have been discovered. Here we evaluate the effects of the orally bioavailable small-molecule IR activator (Compound-2) on metabolic abnormalities associated with type 2 diabetes using a nongenetic mouse model in comparison with the effects of a novel non-thiazolidinedione (nTZD) peroxisome proliferator-activated receptor-γ agonist. Both Compound-2 and nTZD alleviated fasting and postprandial hyperglycemia; accelerated glucose clearance rate; and normalized plasma levels of nonesterified fatty acids, triglycerides, and leptin. Unlike nTZD, which increased body weight gain, and total fat mass, which is a common feature for PPARγ agonists, Compound-2 prevented body weight gain and hypertrophy of brown, and white adipose tissue depots and the development of hepatic steatosis in the mouse model of type 2 diabetes. The effect of the two compounds on proximal steps in insulin signal transduction pathway was analyzed in tissues. Compound-2 enhanced insulin-stimulated phosphorylation of IR tyrosine and/or Akt in the liver, skeletal muscle, and white adipose tissue, whereas nTZD potentiated the phosphorylation of IR and Akt in the adipose tissue only. In conclusion, small-molecule IR activators have unique features as insulin sensitizers and hold potential utility in the treatment of type 2 diabetes and obesity.

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