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

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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Free Sugars Consumption in Canada

Nutrients ◽

10.3390/nu13051471 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1471

Author(s):

Huma Rana ◽

Marie-Claude Mallet ◽

Alejandro Gonzalez ◽

Marie-France Verreault ◽

Sylvie St-Pierre

Keyword(s):

Type 2 Diabetes ◽

Weight Gain ◽

Total Energy ◽

Children And Adolescents ◽

Overweight And Obesity ◽

Free Sugars ◽

Added Sugars ◽

Increased Risk ◽

Baked Products

Free sugars (FS) are associated with a higher risk of dental decay in children and an increased risk of weight gain, overweight and obesity and type 2 diabetes. For this reason, Canada’s Food Guide recommends limiting foods and beverages that contribute to excess free sugars consumption. Estimating FS intakes is needed to inform policies and interventions aimed at reducing Canadians’ consumption of FS. The objective of this study was to estimate FS intake of Canadians using a new method that estimated the free sugars content of foods in the Canadian Nutrient File, the database used in national nutrition surveys. We define FS as sugars present in food products in which the structure has been broken down. We found that 12% of total energy (about 56 g) comes from FS in the diet of Canadians 1 year of age and older (≥1 year). The top four sources were: (1) sugars, syrups, preserves, confectionary, desserts; (2) soft drinks; (3) baked products and (4) juice (without added sugars), and accounted for 60% of total free sugars intake. The results show that efforts need to be sustained to help Canadians, particularly children and adolescents, to reduce their FS intake.

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Depression-related weight change and incident diabetes in a community sample

Scientific Reports ◽

10.1038/s41598-021-92963-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eva Graham ◽

Tristan Watson ◽

Sonya S. Deschênes ◽

Kristian B. Filion ◽

Mélanie Henderson ◽

...

Keyword(s):

Type 2 Diabetes ◽

Weight Loss ◽

Weight Gain ◽

Weight Change ◽

Short Form ◽

Community Sample ◽

Overweight And Obesity ◽

Community Dwelling ◽

Increased Risk

AbstractThis cohort study aimed to compare the incidence of type 2 diabetes in adults with depression-related weight gain, depression-related weight loss, depression with no weight change, and no depression. The study sample included 59,315 community-dwelling adults in Ontario, Canada. Depression-related weight change in the past 12 months was measured using the Composite International Diagnostic Interview—Short Form. Participants were followed for up to 20 years using administrative health data. Cox proportional hazards models compared the incidence of type 2 diabetes in adults with depression-related weight change and in adults with no depression. Adults with depression-related weight gain had an increased risk of type 2 diabetes compared to adults no depression (HR 1.70, 95% CI 1.32–2.20), adults with depression-related weight loss (HR 1.62, 95% CI 1.09–2.42), and adults with depression with no weight change (HR 1.39, 95% CI 1.03–1.86). Adults with depression with no weight change also had an increased risk of type 2 diabetes compared to those with no depression (HR 1.23, 95% CI 1.04–1.45). Associations were stronger among women and persisted after adjusting for attained overweight and obesity. Identifying symptoms of weight change in depression may aid in identifying adults at higher risk of type 2 diabetes and in developing tailored prevention strategies.

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Antipsychotics and glucose metabolism: how brain and body collide

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00164.2018 ◽

2019 ◽

Vol 316 (1) ◽

pp. E1-E15 ◽

Cited By ~ 10

Author(s):

Chantel Kowalchuk ◽

Laura N. Castellani ◽

Araba Chintoh ◽

Gary Remington ◽

Adria Giacca ◽

...

Keyword(s):

Type 2 Diabetes ◽

Weight Gain ◽

Glucose Metabolism ◽

First Generation ◽

Clinical Evidence ◽

Mental Illnesses ◽

Therapeutic Effects ◽

Direct Effects ◽

Increased Risk

Since the serendipitous discovery of the first antipsychotic (AP) drug in the 1950s, APs remain the cornerstone of treatment for schizophrenia. A shift over the past two decades away from first-generation, conventional APs to so-called “atypical” (or 2nd/3rd generation) APs parallels acknowledgment of serious metabolic side-effects associated in particular with these newer agents. As will be reviewed, AP drugs and type 2 diabetes are now inextricably linked, contributing to the three- to fivefold increased risk of type 2 diabetes observed in schizophrenia. However, this association is not straightforward. Biological and lifestyle-related illness factors contribute to the association between type 2 diabetes and metabolic disease independently of AP treatment. In addition, APs have a well-established weight gain propensity which could also account for elevated risk of insulin resistance and type 2 diabetes. However, compelling preclinical and clinical evidence now suggests that these drugs can rapidly and directly influence pathways of glucose metabolism independently of weight gain and even in absence of psychiatric illness. Mechanisms of these direct effects remain poorly elucidated but may involve central and peripheral antagonism of neurotransmitters implicated not only in the therapeutic effects of APs but also in glucose homeostasis, possibly via effects on the autonomic nervous system. The clinical relevance of studying “direct” effects of these drugs on glucose metabolism is underscored by the widespread use of these medications, both on and off label, for a growing number of mental illnesses, extending safety concerns well beyond schizophrenia.

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Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00302.2006 ◽

2007 ◽

Vol 292 (3) ◽

pp. E740-E747 ◽

Cited By ~ 561

Author(s):

S. J. Creely ◽

P. G. McTernan ◽

C. M. Kusminski ◽

ff. M. Fisher ◽

N. F. Da Silva ◽

...

Keyword(s):

Type 2 Diabetes ◽

Adipose Tissue ◽

Protein Expression ◽

Serum Insulin ◽

Human Adipose Tissue ◽

Innate Immune ◽

System Response ◽

Low Grade ◽

Tnf Α

Type 2 diabetes (T2DM) is associated with chronic low-grade inflammation. Adipose tissue (AT) may represent an important site of inflammation. 3T3-L1 studies have demonstrated that lipopolysaccharide (LPS) activates toll-like receptors (TLRs) to cause inflammation. For this study, we 1) examined activation of TLRs and adipocytokines by LPS in human abdominal subcutaneous (AbdSc) adipocytes, 2) examined blockade of NF-κB in human AbdSc adipocytes, 3) examined the innate immune pathway in AbdSc AT from lean, obese, and T2DM subjects, and 4) examined the association of circulating LPS in T2DM subjects. The findings showed that LPS increased TLR-2 protein expression twofold ( P < 0.05). Treatment of AbdSc adipocytes with LPS caused a significant increase in TNF-α and IL-6 secretion (IL-6, Control: 2.7 ± 0.5 vs. LPS: 4.8 ± 0.3 ng/ml; P < 0.001; TNF-α, Control: 1.0 ± 0.83 vs. LPS: 32.8 ± 6.23 pg/ml; P < 0.001). NF-κB inhibitor reduced IL-6 in AbdSc adipocytes (Control: 2.7 ± 0.5 vs. NF-κB inhibitor: 2.1 ± 0.4 ng/ml; P < 0.001). AbdSc AT protein expression for TLR-2, MyD88, TRAF6, and NF-κB was increased in T2DM patients ( P < 0.05), and TLR-2, TRAF-6, and NF-κB were increased in LPS-treated adipocytes ( P < 0.05). Circulating LPS was 76% higher in T2DM subjects compared with matched controls. LPS correlated with insulin in controls ( r = 0.678, P < 0.0001). Rosiglitazone (RSG) significantly reduced both fasting serum insulin levels (reduced by 51%, P = 0.0395) and serum LPS (reduced by 35%, P = 0.0139) in a subgroup of previously untreated T2DM patients. In summary, our results suggest that T2DM is associated with increased endotoxemia, with AT able to initiate an innate immune response. Thus, increased adiposity may increase proinflammatory cytokines and therefore contribute to the pathogenic risk of T2DM.

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The Pathophysiology of Gestational Diabetes Mellitus

International Journal of Molecular Sciences ◽

10.3390/ijms19113342 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3342 ◽

Cited By ~ 112

Author(s):

Jasmine Plows ◽

Joanna Stanley ◽

Philip Baker ◽

Clare Reynolds ◽

Mark Vickers

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Molecular Mechanisms ◽

Overweight And Obesity ◽

Chronic Hyperglycemia ◽

Increased Risk

Gestational diabetes mellitus (GDM) is a serious pregnancy complication, in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. In most cases, this hyperglycemia is the result of impaired glucose tolerance due to pancreatic β-cell dysfunction on a background of chronic insulin resistance. Risk factors for GDM include overweight and obesity, advanced maternal age, and a family history or any form of diabetes. Consequences of GDM include increased risk of maternal cardiovascular disease and type 2 diabetes and macrosomia and birth complications in the infant. There is also a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies worldwide, and this number is set to increase with the escalating obesity epidemic. While several management strategies exist—including insulin and lifestyle interventions—there is not yet a cure or an efficacious prevention strategy. One reason for this is that the molecular mechanisms underlying GDM are poorly defined. This review discusses what is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration.

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Increased hepatic lipogenesis in insulin resistance and Type 2 diabetes is associated with AMPK signalling pathway up-regulation in Psammomys obesus

Bioscience Reports ◽

10.1042/bsr20080141 ◽

2009 ◽

Vol 29 (5) ◽

pp. 283-292 ◽

Cited By ~ 27

Author(s):

Ali Ben Djoudi Ouadda ◽

Emile Levy ◽

Ehud Ziv ◽

Geneviève Lalonde ◽

Alain T. Sané ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Protein Expression ◽

Body Weight Gain ◽

Binding Protein ◽

Regulatory Element ◽

Mrna Levels ◽

Psammomys Obesus ◽

Element Binding Protein

AMPK (AMP-activated protein kinase) has been suggested to be a central player regulating FA (fatty acid) metabolism through its ability to regulate ACC (acetyl-CoA carboxylase) activity. Nevertheless, its involvement in insulin resistance- and TD2 (Type 2 diabetes)-associated dyslipidaemia remains enigmatic. In the present study, we employed the Psammomys obesus gerbil, a well-established model of insulin resistance and TD2, in order to appreciate the contribution of the AMPK/ACC pathway to the abnormal hepatic lipid synthesis and increased lipid accumulation in the liver. Our investigation provided evidence that the development of insulin resistance/diabetic state in P. obesus is accompanied by (i) body weight gain and hyperlipidaemia; (ii) elevations of hepatic ACC-Ser79 phosphorylation and ACC protein levels; (iii) a rise in the gene expression of cytosolic ACC1 concomitant with invariable mitochondrial ACC2; (iv) an increase in hepatic AMPKα-Thr172 phosphorylation and protein expression without any modification in the calculated ratio of phospho-AMPKα to total AMPKα; (v) a stimulation in ACC activity despite increased AMPKα phosphorylation and protein expression; and (vi) a trend of increase in mRNA levels of key lipogenic enzymes [SCD-1 (stearoyl-CoA desaturase-1), mGPAT (mitochondrial isoform of glycerol-3-phosphate acyltransferase) and FAS (FA synthase)] and transcription factors [SREBP-1 (sterol-regulatory-element-binding protein-1) and ChREBP (carbohydrate responsive element-binding protein)]. Altogether, our findings suggest that up-regulation of the AMPK pathway seems to be a natural response in order to reduce lipid metabolism abnormalities, thus supporting the role of AMPK as a promising target for the treatment of TD2-associated dyslipidaemia.

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

Diabetes Care ◽

10.2337/dc06-0254 ◽

2006 ◽

Vol 29 (8) ◽

pp. 1826-1832 ◽

Cited By ~ 125

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

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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.

10.1101/2021.12.05.471325 ◽

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.

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Effect of 10 days of bedrest on metabolic and vascular insulin action: a study in individuals at risk for type 2 diabetes

Journal of Applied Physiology ◽

10.1152/japplphysiol.00545.2009 ◽

2010 ◽

Vol 108 (4) ◽

pp. 830-837 ◽

Cited By ~ 27

Author(s):

Mette P. Sonne ◽

Amra C. Alibegovic ◽

Lise Højbjerre ◽

Allan Vaag ◽

Bente Stallknecht ◽

...

Keyword(s):

Physical Activity ◽

Type 2 Diabetes ◽

Insulin Sensitivity ◽

High Sensitivity ◽

Whole Body ◽

Diabetic Patients ◽

Activity Levels ◽

Type 2 Diabetic Patients ◽

Increased Risk

Physical inactivity is a known risk factor for type 2 diabetes. We studied whole body and forearm insulin sensitivity in subjects at increased risk for type 2 diabetes [persons with low birth weight (LBW group; n = 20) and first-degree relatives to type 2 diabetic patients (FDR group; n = 13)] as well as a control (CON) group ( n = 20) matched for body mass index, age, and physical activity levels before and after 10 days of bedrest. Subjects were studied by hyperinsulinemic isoglycemic clamp combined with arterial and deep venous catheterization of the forearm. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. All groups responded with a decrease in whole body insulin sensitivity in response to bedrest [CON group: 6.8 ± 0.5 to 4.3 ± 0.3 mg·min−1·kg−1( P < 0.0001), LBW group: 6.2 ± 0.5 to 4.3 ± 0.3 mg·min−1·kg−1( P < 0.0001), and FDR group: 4.3 ± 0.7 to 3.1 ± 0.3 mg·min−1·kg−1( P = 0.068)]. The percent decrease was significantly greater in the CON group compared with the FDR group (CON group: 34 ± 4%, LBW group: 27 ± 4%, and FDR group: 10 ± 13%). Forearm insulin-stimulated glucose clearance decreased significantly in the CON and LBW groups in response to bedrest; in the FDR group, clearance was very low before bedrest and no change was observed. Before bedrest, the CON and LBW groups demonstrated a significant increase in FBF during hyperinsulinemia; after bedrest, an increase in FBF was observed only in the CON group. In conclusion, bedrest induced a pronounced reduction in whole body, skeletal muscle, and vascular insulin sensitivity in the CON and LBW groups. The changes were most pronounced in the CON group. In the FDR group, insulin resistance was already present before bedrest, but even this group displayed a high sensitivity to changes in daily physical activity.

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Exercise and type 2 diabetes: molecular mechanisms regulating glucose uptake in skeletal muscle

AJP Advances in Physiology Education ◽

10.1152/advan.00080.2014 ◽

2014 ◽

Vol 38 (4) ◽

pp. 308-314 ◽

Cited By ~ 95

Author(s):

Kristin I. Stanford ◽

Laurie J. Goodyear

Keyword(s):

Type 2 Diabetes ◽

Skeletal Muscle ◽

Glucose Uptake ◽

Molecular Mechanisms ◽

Glucose Transporter ◽

Whole Body ◽

Metabolic Genes ◽

Increase Glucose Uptake ◽

Glucose Transporter Proteins

Exercise is a well-established tool to prevent and combat type 2 diabetes. Exercise improves whole body metabolic health in people with type 2 diabetes, and adaptations to skeletal muscle are essential for this improvement. An acute bout of exercise increases skeletal muscle glucose uptake, while chronic exercise training improves mitochondrial function, increases mitochondrial biogenesis, and increases the expression of glucose transporter proteins and numerous metabolic genes. This review focuses on the molecular mechanisms that mediate the effects of exercise to increase glucose uptake in skeletal muscle.

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