scholarly journals Evaluating the Impact of Different Hypercaloric Diets on Weight Gain, Insulin Resistance, Glucose Intolerance, and its Comorbidities in Rats

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1197 ◽  
Author(s):  
Bernardete F. Melo ◽  
Joana F. Sacramento ◽  
Maria J. Ribeiro ◽  
Claudia S. Prego ◽  
Miguel C. Correia ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Weight Gain ◽  
Animal Models ◽  
High Fat ◽  
Zucker Fatty Rat ◽  
High Sucrose

Animal experimentation has a long history in the study of metabolic syndrome-related disorders. However, no consensus exists on the best models to study these syndromes. Knowing that different diets can precipitate different metabolic disease phenotypes, herein we characterized several hypercaloric rat models of obesity and type 2 diabetes, comparing each with a genetic model, with the aim of identifying the most appropriate model of metabolic disease. The effect of hypercaloric diets (high fat (HF), high sucrose (HSu), high fat plus high sucrose (HFHSu) and high fat plus streptozotocin (HF+STZ) during different exposure times (HF 3 weeks, HF 19 weeks, HSu 4 weeks, HSu 16 weeks, HFHSu 25 weeks, HF3 weeks + STZ) were compared with the Zucker fatty rat. Each model was evaluated for weight gain, fat mass, fasting plasma glucose, insulin and C-peptide, insulin sensitivity, glucose tolerance, lipid profile and liver lipid deposition, blood pressure, and autonomic nervous system function. All animal models presented with insulin resistance and dyslipidemia except the HF+STZ and HSu 4 weeks, which argues against the use of these models as metabolic syndrome models. Of the remaining animal models, a higher weight gain was exhibited by the Zucker fatty rat and wild type rats submitted to a HF diet for 19 weeks. We conclude that the latter model presents a phenotype most consistent with that observed in humans with metabolic disease, exhibiting the majority of the phenotypic features and comorbidities associated with type 2 diabetes in humans.

Abstract 015: Increased 20-HETE Levels Contribute to Impaired Glucose Metabolism and Type 2 Diabetes in Cyp4a14 Knockout Mice Fed on High Fat Diet.

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Varunkumar G Pandey ◽  
Lars Bellner ◽  
Victor Garcia ◽  
Joseph Schragenheim ◽  
Andrew Cohen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Weight Gain ◽  
Blood Glucose ◽  
High Fat Diet ◽  
Plasma Insulin ◽  
High Fat ◽  
Plasma Insulin Levels

20-HETE (20-Hydroxyeicosatetraenoic acid) is a cytochrome P450 ω-hydroxylase metabolite of arachidonic acid that promotes endothelial dysfunction, microvascular remodeling and hypertension. Previous studies have shown that urinary 20-HETE levels correlate with BMI and plasma insulin levels. However, there is no direct evidence for the role of 20-HETE in the regulation of glucose metabolism, obesity and type 2 diabetes mellitus. In this study we examined the effect of 20-SOLA (2,5,8,11,14,17-hexaoxanonadecan-19-yl-20-hydroxyeicosa-6(Z),15(Z)-dienoate), a water-soluble 20-HETE antagonist, on blood pressure, weight gain and blood glucose in Cyp4a14 knockout (Cyp4a14-/-) mice fed high-fat diet (HFD). The Cyp4a14-/- male mice exhibit high vascular 20-HETE levels and display 20-HETE-dependent hypertension. There was no difference in weight gain and fasting blood glucose between Cyp4a14-/- and wild type (WT) on regular chow. When subjected to HFD for 15 weeks, a significant increase in weight was observed in Cyp4a14-/- as compared to WT mice (56.5±3.45 vs. 30.2±0.7g, p<0.05). Administration of 20-SOLA (10mg/kg/day in drinking water) significantly attenuated the weight gain (28.7±1.47g, p<0.05) and normalized blood pressure in Cyp4a14-/- mice on HFD (116±0.3 vs. 172.7±4.6mmHg, p<0.05). HFD fed Cyp4a14-/- mice exhibited hyperglycemia as opposed to normal glucose levels in WT on a HFD (154±1.9 vs. 96.3±3.0 mg/dL, p<0.05). 20-SOLA prevented the HFD-induced hyperglycemia in Cyp4a14-/- mice (91±8mg/dL, p<0.05). Plasma insulin levels were markedly high in Cyp4a14-/- mice vs. WT on HFD (2.66±0.7 vs. 0.58±0.18ng/mL, p<0.05); corrected by the treatment with 20-SOLA (0.69±0.09 ng/mL, p<0.05). Importantly, glucose and insulin tolerance tests showed impaired glucose homeostasis and insulin resistance in Cyp4a14-/- mice on HFD; ameliorated by treatment with 20-SOLA. This novel finding that blockade of 20-HETE actions by 20-SOLA prevents HFD-induced obesity and restores glucose homeostasis in Cyp4a14-/- mice suggests that 20-HETE contributes to obesity, hyperglycemia and insulin resistance in HFD induced metabolic disorder. The molecular mechanisms underlying 20-HETE mediated metabolic dysfunction are being currently explored.

scholarly journals Kill two birds with one stone: making multi-transgenic pre-diabetes mouse models through insulin resistance and pancreatic apoptosis pathogenesis

2017 ◽  
Author(s):  
Siyuan Kong ◽  
Jinxue Ruan ◽  
Kaiyi Zhang ◽  
Bingjun Hu ◽  
Yuzhu Cheng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Transgenic Mice ◽  
Mouse Models ◽  
Early Stage ◽  
Transgenic Animals ◽  
High Fat ◽  
Adipose Tissues ◽  
High Sucrose

Background. Type 2 diabetes, a chronic disease to which susceptibility is hereditary, is characterized by insulin resistance accompanied by defective insulin secretion. Mouse models, especially transgenic mice, play an important role in medical research. However, the transgenic mouse models that have been used in diabetes research are involved with single transgenes, focusing on the insulin gene or its mutants. Thus they mainly provide information related to Type 1 diabetes. Methods. Here, we attempted to focus comprehensively on genes related to pancreatic islet damage, peripheral insulin resistance and related environmental inducing factors by generating single-transgenic mice (CHOP), dual-transgenic mice (hIAPP-CHOP) and triple-transgenic mice (11β-HSD1-hIAPP-CHOP). The latter two types of transgenic animals were induced with high-fat, high-sucrose diets (HFHSD). We evaluated and analyzed the diabetes-related symptoms and the histopathological and immunohistochemical features of the transgenic animals. Results. Specifically, in the triple-transgene animals, the results of intraperitoneal glucose tolerance tests (IPGTT) began to change 60 days after induction (p<0.001). After 190 days of induction, the body weights (p<0.01) and plasma glucose levels of the animals in the Tg group were higher than those of the animals in the Nc group. After the mice were sacrificed, large amounts of lipid were found deposited in the adipose tissues (p<0.01) and ectopically deposited in the non-adipose tissues (p<0.05 or 0.01) of the animals in the Tg HFHSD group. The weights of the kidneys and hearts of the Tg animals were significantly increased (p<0.01). Serum C-P was decreased due to transgene effects, and insulin levels were increased due to the effects of the high-fat high-sucrose diet in the Tg HFHSD group, indicating that damaged insulin secretion and insulin resistance hyperinsulinemia existed simultaneously in these animals. The serum corticosterone levels of the animals in the Tg group were slightly higher than those of the Nc animals due to the effects of the 11βHSD-1 transgene and obesity. In the Tg HFHSD group, hepatic adipose deposition was more severe and the pancreatic islet area was enlarged under compensation, accompanying apoptosis. In the Tg ControlD group, hepatic adipose deposition was also severe, pancreatic islets were damaged, and their areas were decreased (p<0.05), and apoptosis of pancreatic cells occurred. Taken together, these data show that the transgenes led to early-stage pathological changes characteristic of type 2 diabetes in the triple-transgene HFHSD group. The disease of triple-transgenic mice was more severe than that of dual or single-transgenic mice. Conclusion. The use of multi-transgenes involved in insulin resistance and pancreatic apoptosis is a better way to generate polygene-related early-stage diabetes models.

scholarly journals Athrixia phylicoides tea infusion (bushman tea) improves adipokine balance, glucose homeostasis and lipid parameters in a diet-induced metabolic syndrome rat model

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Madigoahle A. M. Mokwena ◽  
Godwill Azeh Engwa ◽  
Benedicta N. Nkeh-Chungag ◽  
Constance R. Sewani-Rusike
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Weight Gain ◽  
Glucose Homeostasis ◽  
Visceral Fat ◽  
Tea Infusion ◽  
Glut 4 ◽  
Athrixia Phylicoides

Abstract Background Central obesity and insulin resistance are associated with metabolic syndrome (MetS) which is aggravated by diet and sedentary lifestyle. Athrixia phylicoides (AP) is reported by rural communities to have medicinal benefits associated with MetS such as obesity and type 2 diabetes. This study was aimed to investigate the effects of AP on diet-induced MetS in Wistar rats to validate its ethnopharmacological use. Methods AP was profiled for phytochemicals by LC-MS. After induction of MetS with high energy diet (HED), 30 male rats were divided into five treatment groups (n = 6): normal diet control, HED control, HED + AP 50 mg/Kg BW, HED + AP 100 mg/Kg BW and HED + 50 mg/Kg BW metformin. The rats were treated daily for 8 weeks orally after which weight gain, visceral fat, total cholesterol, free fatty acids (FFAs) and adipokine regulation; leptin: adiponectin ratio (LAR) were assessed. Also, glucose homeostatic parameters including fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glucose transporter 4 (GLUT 4), insulin and homeostatic model assessment of insulin resistance (HOMA-IR) were determined. Results Findings showed that AP was rich in polyphenols. The HED control group showed derangements of the selected blood parameters of MetS. AP reversed diet-induced weight gain by reducing visceral fat, total blood cholesterol and circulating FFAs (p ≤ 0.05). Treatment with AP improved adipokine regulation depicted by reduced LAR (p<0.05). Treatment with AP improved parameters of glucose homeostasis as demonstrated by reduced FBG and HOMA-IR (p ≤ 0.05) and increased GLUT 4 (p<0.05). Conclusion Athrixia phylicoides tea infusion was shown to possess anti-obesity and anti-inflammatory properties, improved glucose uptake and reduce insulin resistance in diet-induced MetS in rats which could be attributed to its richness in polyphenols. Therefore, AP could have potential benefits against type 2 diabetes and obesity which are components of MetS validating its ethnopharmacological use.

scholarly journals Kill two birds with one stone: making multi-transgenic pre-diabetes mouse models through insulin resistance and pancreatic apoptosis pathogenesis

2017 ◽  
Author(s):  
Siyuan Kong ◽  
Jinxue Ruan ◽  
Kaiyi Zhang ◽  
Bingjun Hu ◽  
Yuzhu Cheng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Transgenic Mice ◽  
Mouse Models ◽  
Early Stage ◽  
Transgenic Animals ◽  
High Fat ◽  
Adipose Tissues ◽  
High Sucrose

Background. Type 2 diabetes, a chronic disease to which susceptibility is hereditary, is characterized by insulin resistance accompanied by defective insulin secretion. Mouse models, especially transgenic mice, play an important role in medical research. However, the transgenic mouse models that have been used in diabetes research are involved with single transgenes, focusing on the insulin gene or its mutants. Thus they mainly provide information related to Type 1 diabetes. Methods. Here, we attempted to focus comprehensively on genes related to pancreatic islet damage, peripheral insulin resistance and related environmental inducing factors by generating single-transgenic mice (CHOP), dual-transgenic mice (hIAPP-CHOP) and triple-transgenic mice (11β-HSD1-hIAPP-CHOP). The latter two types of transgenic animals were induced with high-fat, high-sucrose diets (HFHSD). We evaluated and analyzed the diabetes-related symptoms and the histopathological and immunohistochemical features of the transgenic animals. Results. Specifically, in the triple-transgene animals, the results of intraperitoneal glucose tolerance tests (IPGTT) began to change 60 days after induction (p<0.001). After 190 days of induction, the body weights (p<0.01) and plasma glucose levels of the animals in the Tg group were higher than those of the animals in the Nc group. After the mice were sacrificed, large amounts of lipid were found deposited in the adipose tissues (p<0.01) and ectopically deposited in the non-adipose tissues (p<0.05 or 0.01) of the animals in the Tg HFHSD group. The weights of the kidneys and hearts of the Tg animals were significantly increased (p<0.01). Serum C-P was decreased due to transgene effects, and insulin levels were increased due to the effects of the high-fat high-sucrose diet in the Tg HFHSD group, indicating that damaged insulin secretion and insulin resistance hyperinsulinemia existed simultaneously in these animals. The serum corticosterone levels of the animals in the Tg group were slightly higher than those of the Nc animals due to the effects of the 11βHSD-1 transgene and obesity. In the Tg HFHSD group, hepatic adipose deposition was more severe and the pancreatic islet area was enlarged under compensation, accompanying apoptosis. In the Tg ControlD group, hepatic adipose deposition was also severe, pancreatic islets were damaged, and their areas were decreased (p<0.05), and apoptosis of pancreatic cells occurred. Taken together, these data show that the transgenes led to early-stage pathological changes characteristic of type 2 diabetes in the triple-transgene HFHSD group. The disease of triple-transgenic mice was more severe than that of dual or single-transgenic mice. Conclusion. The use of multi-transgenes involved in insulin resistance and pancreatic apoptosis is a better way to generate polygene-related early-stage diabetes models.

scholarly journals Time-of-Day-Dependent Effects of Bromocriptine to Ameliorate Vascular Pathology and Metabolic Syndrome in SHR Rats Held on High Fat Diet

2021 ◽  
Vol 22 (11) ◽  
pp. 6142
Author(s):  
Michael Ezrokhi ◽  
Yahong Zhang ◽  
Shuqin Luo ◽  
Anthony H. Cincotta
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
High Fat Diet ◽  
Nitrosative Stress ◽  
Time Of Day ◽  
Vascular Pathology ◽  
Mrna Levels ◽  
High Fat ◽  
Nadph Oxidase 4

The treatment of type 2 diabetes patients with bromocriptine-QR, a unique, quick release micronized formulation of bromocriptine, improves glycemic control and reduces adverse cardiovascular events. While the improvement of glycemic control is largely the result of improved postprandial hepatic glucose metabolism and insulin action, the mechanisms underlying the drug’s cardioprotective effects are less well defined. Bromocriptine is a sympatholytic dopamine agonist and reduces the elevated sympathetic tone, characteristic of metabolic syndrome and type 2 diabetes, which potentiates elevations of vascular oxidative/nitrosative stress, known to precipitate cardiovascular disease. Therefore, this study investigated the impact of bromocriptine treatment upon biomarkers of vascular oxidative/nitrosative stress (including the pro-oxidative/nitrosative stress enzymes of NADPH oxidase 4, inducible nitric oxide (iNOS), uncoupled endothelial nitric oxide synthase (eNOS), the pro-inflammatory/pro-oxidative marker GTP cyclohydrolase 1 (GTPCH 1), and the pro-vascular health enzyme, soluble guanylate cyclase (sGC) as well as the plasma level of thiobarbituric acid reactive substances (TBARS), a circulating marker of systemic oxidative stress), in hypertensive SHR rats held on a high fat diet to induce metabolic syndrome. Inasmuch as the central nervous system (CNS) dopaminergic activities both regulate and are regulated by CNS circadian pacemaker circuitry, this study also investigated the time-of-day-dependent effects of bromocriptine treatment (10 mg/kg/day at either 13 or 19 h after the onset of light (at the natural waking time or late during the activity period, respectively) among animals held on 14 h daily photoperiods for 16 days upon such vascular biomarkers of vascular redox state, several metabolic syndrome parameters, and mediobasal hypothalamic (MBH) mRNA expression levels of neuropeptides neuropeptide Y (NPY) and agouti-related protein (AgRP) which regulate the peripheral fuel metabolism and of mRNA expression of other MBH glial and neuronal cell genes that support such metabolism regulating neurons in this model system. Such bromocriptine treatment at ZT 13 improved (reduced) biomarkers of vascular oxidative/nitrosative stress including plasma TBARS level, aortic NADPH oxidase 4, iNOS and GTPCH 1 levels, and improved other markers of coupled eNOS function, including increased sGC protein level, relative to controls. However, bromocriptine treatment at ZT 19 produced no improvement in either coupled eNOS function or sGC protein level. Moreover, such ZT 13 bromocriptine treatment reduced several metabolic syndrome parameters including fasting insulin and leptin levels, as well as elevated systolic and diastolic blood pressure, insulin resistance, body fat store levels and liver fat content, however, such effects of ZT 19 bromocriptine treatment were largely absent versus control. Finally, ZT 13 bromocriptine treatment reduced MBH NPY and AgRP mRNA levels and mRNA levels of several MBH glial cell/neuronal genes that code for neuronal support/plasticity proteins (suggesting a shift in neuronal structure/function to a new metabolic control state) while ZT 19 treatment reduced only AgRP, not NPY, and was with very little effect on such MBH glial cell genes expression. These findings indicate that circadian-timed bromocriptine administration at the natural circadian peak of CNS dopaminergic activity (that is diminished in insulin resistant states), but not outside this daily time window when such CNS dopaminergic activity is naturally low, produces widespread improvements in biomarkers of vascular oxidative stress that are associated with the amelioration of metabolic syndrome and reductions in MBH neuropeptides and gene expressions known to facilitate metabolic syndrome. These results of such circadian-timed bromocriptine treatment upon vascular pathology provide potential mechanisms for the observed marked reductions in adverse cardiovascular events with circadian-timed bromocriptine-QR therapy (similarly timed to the onset of daily waking as in this study) of type 2 diabetes subjects and warrant further investigations into related mechanisms and the potential application of such intervention to prediabetes and metabolic syndrome patients as well.

scholarly journals The effects of metformin plus sulfonylurea therapy on clinical features of the metabolic syndrome

2010 ◽  
Vol 63 (9-10) ◽  
pp. 611-615 ◽  
Author(s):  
Branka Koprivica ◽  
Teodora Beljic-Zivkovic ◽  
Tatjana Ille
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Body Mass Index ◽  
Waist Circumference ◽  
Glycemic Control ◽  
Body Mass ◽  
Combined Therapy

Introduction. Insulin resistance is a well-known leading factor in the development of metabolic syndrome. The aim of this study was to evaluate metabolic effects of metformin added to sulfonylurea in unsuccessfully treated type 2 diabetic patients with metabolic syndrome. Material and methods. A group of thirty subjects, with type 2 diabetes, secondary sulfonylurea failure and metabolic syndrome were administered the combined therapy of sulfonylurea plus metformin for six months. Metformin 2000 mg/d was added to previously used sulfonylurea agent in maximum daily dose. Antihypertensive and hypolipemic therapy was not changed. The following parameters were assessed at the beginning and after six months of therapy: glycemic control, body mass index, waist circumference, blood pressure, triglycerides, total cholesterol and its fractions, homeostatic models for evaluation of insulin resistance and secretion (HOMA R, HOMA B) and C- peptide. Results. Glycemic control was significantly improved after six months of the combined therapy: (fasting 7.89 vs. 10.61 mmol/l. p<0.01; postprandial 11.12 vs. 12.61 mmol/l. p<0.01, p<0.01; glycosylated hemoglobin 6.81 vs. 8.83%. p<0.01). the body mass index and waist circumference were significantly lower (26.7 vs. 27.8 kg/m2, p<0.01 and 99.7 vs. 101.4 cm for men, p<0.01; 87.2 vs. 88.5 for women, p<0.01). Fasting plasma triglycerides decreased from 3.37 to 2.45 mmol/l (p<0.001) and HOMA R from 7.04 to 5.23 (p<0.001). No treatment effects were observed on blood pressure, cholesterol, and residual insulin secretion. Conclusion. Administration of metformin in type 2 diabetes with metabolic syndrome decreased cardiovascular risk factors by reducing glycemia, triglycerides, BMI, central obesity and insulin resistance.

scholarly journals Spontaneous Type 2 Diabetic Rodent Models

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yang-wei Wang ◽  
Guang-dong Sun ◽  
Jing Sun ◽  
Shu-jun Liu ◽  
Ji Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Health Care ◽  
Animal Models ◽  
Rodent Models ◽  
Advantages And Disadvantages ◽  
Characteristic Features ◽  
Type 2 Diabetic

Diabetes mellitus, especially type 2 diabetes (T2DM), is one of the most common chronic diseases and continues to increase in numbers with large proportion of health care budget being used. Many animal models have been established in order to investigate the mechanisms and pathophysiologic progress of T2DM and find effective treatments for its complications. On the basis of their strains, features, advantages, and disadvantages, various types of animal models of T2DM can be divided into spontaneously diabetic models, artificially induced diabetic models, and transgenic/knockout diabetic models. Among these models, the spontaneous rodent models are used more frequently because many of them can closely describe the characteristic features of T2DM, especially obesity and insulin resistance. In this paper, we aim to investigate the current available spontaneous rodent models for T2DM with regard to their characteristic features, advantages, and disadvantages, and especially to describe appropriate selection and usefulness of different spontaneous rodent models in testing of various new antidiabetic drugs for the treatment of type 2 diabetes.

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