Melatonin supplementation plus exercise behavior ameliorate insulin resistance, hypertension and fatigue in a rat model of type 2 diabetes mellitus

2017 ◽  
Vol 92 ◽  
pp. 606-614 ◽  
Author(s):  
Md. Mahbubur Rahman ◽  
Han-Sol Kwon ◽  
Myung-Jin Kim ◽  
Hyeon-Kyu Go ◽  
Min-Ho Oak ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Rat Model ◽  
Exercise Behavior ◽  
Ameliorate Insulin Resistance

scholarly journals Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance via PTEN-mediated crosstalk between the PI3K/Akt and Erk/MAPKs signaling pathways in the skeletal muscles of db/db mice

2020 ◽  
Author(s):  
Guang Chen ◽  
Xiao-yan Fan ◽  
Xiao-peng Zheng ◽  
Yue-lei Jin ◽  
Ying Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Stem Cells ◽  
Type 2 Diabetes Mellitus ◽  
Human Umbilical Cord ◽  
Tail Vein Injection ◽  
Ameliorate Insulin Resistance

Abstract Background: Globally, 1 in 11 adults have diabetes mellitus and 90% of the cases are type 2 diabetes mellitus. Asia is the epicenter of this global type 2 diabetes mellitus epidemic. Type 2 diabetes mellitus and its complications have contributed significantly to the burden of mortality and disability worldwide. Insulin resistance is a central defect in type 2 diabetes mellitus, and although multiple drugs have been developed to ameliorate insulin resistance, the limitations and accompanying side effects cannot be ignored. Thus more effective methods are required to improve insulin resistance. Methods: In the current study, db/m and db/db mice were injected with human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) via tail vein injection, intraperitoneal injection and skeletal muscle injection. Body weight, fasting blood glucose and the survival rates were monitored. Furthermore, the anti-insulin resistance effects and potential mechanisms of transplanted HUC-MSCs were investigated in db/db mice in vivo. Results: The results showed that HUC-MSC transplantation by skeletal muscle injection was safer compared with tail vein injection and intraperitoneal injection, and the survival rate reached 100% in the skeletal muscle injection transplanted mice. HUC-MSCs can stabilize localization and differentiation in skeletal muscle tissue and significantly ameliorate insulin resistance. Potential regulatory mechanisms are associated with downregulation of inflammation; regulating the balance between PI3K/Akt and ERK/MAPK signaling pathway via PTEN, but was not associated with the IGF-1/IGF-1R signaling pathway. Conclusions: These results suggest HUC-MSC transplantation may be a novel therapeutic direction to prevent insulin resistance and increase insulin sensitivity, and skeletal muscle injection was the safest and most effective way.

scholarly journals Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance via PTEN-mediated crosstalk between the PI3K/Akt and Erk/MAPKs signaling pathways in the skeletal muscles of db/db mice

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Guang Chen ◽  
Xiao-yan Fan ◽  
Xiao-peng Zheng ◽  
Yue-lei Jin ◽  
Ying Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Stem Cells ◽  
Type 2 Diabetes Mellitus ◽  
Human Umbilical Cord ◽  
Tail Vein Injection ◽  
Ameliorate Insulin Resistance

Abstract Background Globally, 1 in 11 adults have diabetes mellitus, and 90% of the cases are type 2 diabetes mellitus. Insulin resistance is a central defect in type 2 diabetes mellitus, and although multiple drugs have been developed to ameliorate insulin resistance, the limitations and accompanying side effects cannot be ignored. Thus, more effective methods are required to improve insulin resistance. Methods In the current study, db/m and db/db mice were injected with human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) via tail vein injection, intraperitoneal injection, and skeletal muscle injection. Body weight, fasting blood glucose, and the survival rates were monitored. Furthermore, the anti-insulin resistance effects and potential mechanisms of transplanted HUC-MSCs were investigated in db/db mice in vivo. Results The results showed that HUC-MSC transplantation by skeletal muscle injection was safer compared with tail vein injection and intraperitoneal injection, and the survival rate reached 100% in the skeletal muscle injection transplanted mice. HUC-MSCs can stabilize localization and differentiation in skeletal muscle tissue and significantly ameliorate insulin resistance. Potential regulatory mechanisms are associated with downregulation of inflammation, regulating the balance between PI3K/Akt and ERK/MAPK signaling pathway via PTEN, but was not associated with the IGF-1/IGF-1R signaling pathway. Conclusions These results suggest HUC-MSC transplantation may be a novel therapeutic direction to prevent insulin resistance and increase insulin sensitivity, and skeletal muscle injection was the safest and most effective way.

scholarly journals Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance via PTEN-mediated crosstalk between the PI3K/Akt and Erk/MAPKs signaling pathways in the skeletal muscles of db/db mice

2020 ◽  
Author(s):  
Guang Chen ◽  
Xiao-yan Fan ◽  
Xiao-peng Zheng ◽  
Yue-lei Jin ◽  
Ying Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Stem Cells ◽  
Type 2 Diabetes Mellitus ◽  
Human Umbilical Cord ◽  
Tail Vein Injection ◽  
Ameliorate Insulin Resistance

Abstract Background: Globally, 1 in 11 adults have diabetes mellitus and 90% of the cases are type 2 diabetes mellitus. Insulin resistance is a central defect in type 2 diabetes mellitus, and although multiple drugs have been developed to ameliorate insulin resistance, the limitations and accompanying side effects cannot be ignored. Thus more effective methods are required to improve insulin resistance. Methods: In the current study, db/m and db/dbmice were injected with human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) via tail vein injection, intraperitoneal injection and skeletal muscle injection. Body weight, fasting blood glucose and the survival rates were monitored. Furthermore, the anti-insulin resistance effects and potential mechanisms of transplanted HUC-MSCs were investigated in db/db mice in vivo. Results: The results showed that HUC-MSC transplantation by skeletal muscle injection was safer compared with tail vein injection and intraperitoneal injection, and the survival rate reached 100% in the skeletal muscle injection transplanted mice. HUC-MSCs can stabilize localization and differentiation in skeletal muscle tissue and significantly ameliorate insulin resistance. Potential regulatory mechanisms are associated with downregulation of inflammation; regulating the balance between PI3K/Akt and ERK/MAPK signaling pathway via PTEN, but was not associated with the IGF-1/IGF-1R signaling pathway. Conclusions: These results suggest HUC-MSC transplantation may be a novel therapeutic direction to prevent insulin resistance and increase insulin sensitivity, and skeletal muscle injection was the safest and most effective way.

scholarly journals Development and characterization of a novel rat model of type 2 diabetes mellitus: the UC Davis type 2 diabetes mellitus UCD-T2DM rat

2008 ◽  
Vol 295 (6) ◽  
pp. R1782-R1793 ◽  
Author(s):  
Bethany P. Cummings ◽  
Erin K. Digitale ◽  
Kimber L. Stanhope ◽  
James L. Graham ◽  
Denis G. Baskin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Tolerance ◽  
Rat Model ◽  
Age Of Onset ◽  
Female Rats ◽  
Β Cell

The prevalence of type 2 diabetes (T2DM) is increasing, creating a need for T2DM animal models for the study of disease pathogenesis, prevention, and treatment. The purpose of this project was to develop a rat model of T2DM that more closely models the pathophysiology of T2DM in humans. The model was created by crossing obese Sprague-Dawley rats with insulin resistance resulting from polygenic adult-onset obesity with Zucker diabetic fatty-lean rats that have a defect in pancreatic β-cell function but normal leptin signaling. We have characterized the model with respect to diabetes incidence; age of onset; longitudinal measurements of glucose, insulin, and lipids; and glucose tolerance. Longitudinal fasting glucose and insulin data demonstrated progressive hyperglycemia (with fasting and fed glucose concentrations >250 and >450 mg/dl, respectively) after onset along with hyperinsulinemia resulting from insulin resistance at onset followed by a progressive decline in circulating insulin concentrations, indicative of β-cell decompensation. The incidence of diabetes in male and female rats was 92 and 43%, respectively, with an average age of onset of 6 mo in males and 9.5 mo in females. Results from intravenous glucose tolerance tests, pancreas immunohistochemistry, and islet insulin content further support a role for β-cell dysfunction in the pathophysiology of T2DM in this model. Diabetic animals also exhibit glycosuria, polyuria, and hyperphagia. Thus diabetes in the UC Davis-T2DM rat is more similar to clinical T2DM in humans than in other existing rat models and provides a useful model for future studies of the pathophysiology, treatment, and prevention of T2DM.

scholarly journals DECREASEMENT OF LYSOPHOSPHATIDYLCHOLINE LEVEL, NF-KB EXPRESSION, INTIMA MEDIA THICKNESS AND IMPROVEMENT OF INSULIN RESISTANCE BY DARAPLADIB TREATMENT: IN VIVO STUDIES OF TYPE 2 DIABETES MELLITUS SPRAGUE-DAWLEY RAT MODEL

2017 ◽  
Vol 10 (12) ◽  
pp. 362
Author(s):  
Titin Andri Wihastuti ◽  
Dinda Zahra Putri Andiyani ◽  
Sri Andarini ◽  
Teuku Heriansyah
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Rat Model ◽  
Intima Media Thickness ◽  
Aortic Tissue ◽  
Sprague Dawley ◽  
Media Thickness

Objective: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme with several pro-inflammatory properties that involved in pathogenesis of atherosclerosis, but some investigation shows controversial views regarding its biological role. We examined the effect of selective inhibitor of Lp-PLA2 (darapladib) to the inflammation marker, intima-media thickness (IMT), and insulin resistance (IR) of type 2 diabetes mellitus (T2DM) rat model. This study aimed to measure lysophosphatidylcholine (lyso-PC) in serum and aortic tissue, nuclear factor kappa B (NF-κB) expression, IMT, and IR with darapladib treatment in a T2DM rat model.Methods: 30 Sprague-Dawley rats were randomly divided into normal group, T2DM group and T2DM with darapladib treatment. Induction of T2DM was done by giving high-fat diet and low dose injection of streptozotocin. Blood glucose level and insulin plasma concentration were measured to calculate IR. 8 weeks and 16 weeks after treatment, we compared lyso-PC level, NF-κB expression, and IMT.Results: Darapladib significantly decreased lyso-PC level, NF-κB expression, and IMT at two serial treatments. Darapladib treatment group exhibited significant reduction of IR (0.64±0.11 vs. 2.07±0.16, at 8 weeks; and 0.93±0.08 vs. 6.48±0.55 at 16 weeks) compared with T2DM group.Conclusions: These data suggested that Lp-PLA2 played a role in inflammation process, atherosclerosis, and IR occurring in metabolic disorder.

scholarly journals Effect of sitagliptin on expression of skeletal muscle peroxisome proliferator-activated receptor γ coactivator-1α and irisin in a rat model of type 2 diabetes mellitus

2020 ◽  
Vol 48 (5) ◽  
pp. 030006051988556
Author(s):  
Yuntao Liu ◽  
Feng Xu ◽  
Pan Jiang
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Rat Model ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Tnf Α

Objective To evaluate the effect of sitagliptin on skeletal muscle expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), irisin, and phosphoadenylated adenylate activated protein kinase (p-AMPK) in a rat model of type 2 diabetes mellitus (T2DM). Methods A high-fat diet/streptozotocin T2DM rat model was established. Rats were divided into T2DM, low-dose sitagliptin (ST1), high-dose sitagliptin (ST2), and normal control groups (NC). PGC-1α, irisin, and p-AMPK protein levels in skeletal muscle were measured by western blot, and PCG-1α and Fndc5 mRNA levels were assessed by reverse transcription-polymerase chain reaction. Results Fasting plasma glucose (FPG), fasting insulin (FIns), homeostatic model assessment-insulin resistance (HOMA-IR), and tumor necrosis factor-α (TNF-α) were significantly up-regulated in the T2DM compared with the other groups, and FPG, FIns, total cholesterol, triglycerides, TNF-α, and HOMA-IR were significantly down-regulated in the ST2 compared with the ST1 group. PGC-1α, irisin, and p-AMPK expression levels decreased successively in the ST2, ST1, and DM groups compared with the NC, and were all significantly up-regulated in the ST2 compared with the ST1 group. Conclusion Down-regulation of PGC-1α and irisin in skeletal muscle may be involved in T2DM. Sitagliptin can dose-dependently up-regulate PCG-1α and irisin, potentially improving insulin resistance and glycolipid metabolism and inhibiting inflammation.

Khat (Catha edulis) Exacerbate Insulin Resistance in A High-Fat Diet/Streptozotocin-Induced Rat Model of Type 2 Diabetes Mellitus

Metabolism ◽  
2021 ◽  
Vol 116 ◽  
pp. 154546
Author(s):  
Mohammed A. Alshawsh ◽  
Abdulsamad Alsalahi ◽  
Zahurin Mohamed ◽  
Nelli Giribabu ◽  
Zamri Chik
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Rat Model ◽  
High Fat Diet ◽  
High Fat ◽  
Catha Edulis

scholarly journals Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance via PTEN-mediated crosstalk between the PI3K/Akt and Erk/MAPKs signaling pathways in the skeletal muscles of db/db mice

2020 ◽  
Author(s):  
Guang Chen ◽  
Xiao-yan Fan ◽  
Xiao-peng Zheng ◽  
Yue-lei Jin ◽  
Ying Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Stem Cells ◽  
Type 2 Diabetes Mellitus ◽  
Human Umbilical Cord ◽  
Tail Vein Injection ◽  
Ameliorate Insulin Resistance

Abstract Background: Globally, 1 in 11 adults have diabetes mellitus and 90% of the cases are type 2 diabetes mellitus. Asia is the epicenter of this global type 2 diabetes mellitus epidemic. Type 2 diabetes mellitus and its complications have contributed significantly to the burden of mortality and disability worldwide. Insulin resistance is a central defect in type 2 diabetes mellitus, and although multiple drugs have been developed to ameliorate insulin resistance, the limitations and accompanying side effects cannot be ignored. Thus more effective methods are required to improve insulin resistance. Methods: In the current study, db/m and db/db mice were injected with human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) via tail vein injection, intraperitoneal injection and skeletal muscle injection. Body weight, fasting blood glucose and the survival rates were monitored. Furthermore, the anti-insulin resistance effects and potential mechanisms of transplanted HUC-MSCs were investigated in db/db mice in vivo . Results: The results showed that HUC-MSC transplantation by skeletal muscle injection was safer compared with tail vein injection and intraperitoneal injection, and the survival rate reached 100% in the skeletal muscle injection transplanted mice. HUC-MSCs can stabilize localization and differentiation in skeletal muscle tissue and significantly ameliorate insulin resistance. Potential regulatory mechanisms are associated with downregulation of inflammation; regulating the balance between PI3K/Akt and ERK/MAPK signaling pathway via PTEN, but was not associated with the IGF-1/IGF-1R signaling pathway. Conclusions: These results suggest HUC-MSC transplantation may be a novel therapeutic direction to prevent insulin resistance and increase insulin sensitivity, and skeletal muscle injection was the safest and most effective way.

Sign in / Sign up

Export Citation Format

Share Document