scholarly journals I-M-150847, a novel GLP-1 and GIP receptor dual agonist, reduces body weight gain and improves glycemic control in the rodent model of type 2 diabetes and obesity.

2021 ◽  
Author(s):  
PRASENJIT MITRA ◽  
Rathin Bauri ◽  
Shilpak Bele ◽  
Jhansi Edelli ◽  
Sourav Dasadhikari ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Single Amino Acid ◽  
The Novel ◽  
Diabetes And Obesity ◽  
Dual Agonist ◽  
Gip Receptor

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.

scholarly journals Chromium Picolinate Supplementation Attenuates Body Weight Gain and Increases Insulin Sensitivity in Subjects With Type 2 Diabetes

Diabetes Care ◽  
2006 ◽  
Vol 29 (8) ◽  
pp. 1826-1832 ◽  
Author(s):  
J. Martin ◽  
Z. Q. Wang ◽  
X. H. Zhang ◽  
D. Wachtel ◽  
J. Volaufova ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Body Weight Gain ◽  
Chromium Picolinate

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

Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 4658-4666 ◽  
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.

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

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.

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

2013 ◽  
Vol 15 (3) ◽  
pp. 202-214 ◽  
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

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

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 5259-5268 ◽  
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.

scholarly journals GIP receptor antagonist treatment causes weight loss in ovariectomized high fat diet-fed mice

2021 ◽  
Author(s):  
Geke Aline Boer ◽  
Jenna Hunt ◽  
Maria Gabe ◽  
Johanne Windeløv ◽  
Alexander Sparre-Ulricht ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Pharmacokinetic Profile ◽  
High Fat ◽  
Ovariectomized Mice ◽  
Gip Receptor

Background and purpose The incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), secreted by the enteroendocrine K-cells in the proximal intestine, may regulate lipid metabolism and adiposity but its exact role in these processes is unclear. Experimental approach We characterized in vitro and in vivo antagonistic properties of a novel GIP analogue, mGIPAnt-1. We further assessed the in vivo pharmacokinetic profile of this antagonist, as well as its ability to affect high-fat diet (HFD)-induced body weight gain in ovariectomized mice during an 8-week treatment period. Key results mGIPAnt-1 showed competitive antagonistic properties to the GIP receptor (GIPR) in vitro as it inhibited GIP-induced cAMP accumulation in COS-7 cells. Furthermore, mGIPAnt-1 was capable of inhibiting GIP-induced glucoregulatory and insulinotropic effects in vivo and has a favourable pharmacokinetic profile with a half-life of 7.2 hours in C57Bl6 female mice. Finally, sub-chronic treatment with mGIPAnt-1 in ovariectomized HFD mice resulted in a reduction of body weight and fat mass. Conclusion and Implications mGIPAnt-1 successfully inhibited acute GIP-induced effects in vitro and in vivo and sub-chronically induces resistance to HFD-induced weight gain in ovariectomized mice. Our results support the development of GIP antagonists for the therapy of obesity.

scholarly journals Exercise prevents whole-body type 2 diabetes risk factors better than estradiol replacement in rats

2021 ◽  
Author(s):  
Luke J. Fritsch ◽  
Skylar J. McCaulley ◽  
Colton R. Johnson ◽  
Nicholaus J. Lawson ◽  
Brittany K. Gorres-Martens
Keyword(s):  
Type 2 Diabetes ◽  
Weight Gain ◽  
Protein Expression ◽  
Molecular Mechanisms ◽  
Body Weight Gain ◽  
Serum Insulin ◽  
Whole Body ◽  
Body Type ◽  
Increased Risk

Introduction: The absence of estrogens in postmenopausal women is linked to an increased risk of type 2 diabetes (T2D), and estradiol replacement can decrease this risk. Notably, exercise can also treat and prevent T2D. This study seeks to understand the molecular mechanisms by which estradiol and exercise induce their beneficial effects via assessing whole-body and cellular changes. Methods: Female Wistar rats were ovariectomized and fed a high-fat diet for 10 weeks and divided into the following 4 experimental groups: 1) no treatment (control), 2) exercise (Ex), 3) estradiol replacement, and 4) Ex+estradiol. Results: Both Ex and estradiol decreased the total body weight gain. However, only exercise effectively reduced the white adipose tissue (WAT) weight gain, food intake, blood glucose levels and serum insulin levels. At the molecular level, exercise increased the non-insulin stimulated pAkt levels in the WAT. In the liver, estradiol increased the protein expression of ACC and FAS, and estradiol decreased the hepatic protein expression of LPL. In the WAT, estradiol and exercise increased the protein expression of ATGL. Conclusion: Exercise provides better protection against T2D when considering whole body measurements, which may be due to increased non-insulin stimulated pAkt in the WAT. However, at the cellular level, several molecular changes in fat metabolism and fat storage occurred in the liver and WAT with estradiol treatment.

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