scholarly journals Effects of a Novel Glucokinase Activator, HMS5552, on Glucose Metabolism in a Rat Model of Type 2 Diabetes Mellitus

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Ping Wang ◽  
Huili Liu ◽  
Li Chen ◽  
Yingli Duan ◽  
Qunli Chen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Whole Body ◽  
Glucokinase Activator ◽  
Liver And Pancreas

Glucokinase (GK) plays a critical role in the control of whole-body glucose homeostasis. We investigated the possible effects of a novel glucokinase activator (GKA), HMS5552, to the GK in rats with type 2 diabetes mellitus (T2DM). Male Sprague-Dawley (SD) rats were divided into four groups: control group, diabetic group, low-dose (10 mg/kg) HMS5552-treated diabetic group (HMS-L), and high-dose (30 mg/kg) HMS5552-treated diabetic group (HMS-H). HMS5552 was administered intragastrically to the T2DM rats for one month. The levels of total cholesterol, triglyceride, fasting plasma insulin (FINS), and glucagon (FG) were determined, and an oral glucose tolerance test was performed. The expression patterns of proteins and genes associated with insulin resistance and GK activity were assayed. Compared with diabetic rats, the FINS level was significantly decreased in the HMS5552-treated diabetic rats. HMS5552 treatment significantly lowered the blood glucose levels and improved GK activity and insulin resistance. The immunohistochemistry, western blot, and semiquantitative RT-PCR results further demonstrated the effects of HMS5552 on the liver and pancreas. Our data suggest that the novel GKA, HMS5552, exerts antidiabetic effects on the liver and pancreas by improving GK activity and insulin resistance, which holds promise as a novel drug for the treatment of T2DM patients.

scholarly journals IMPROVEMENT IN OXIDATIVE STRESS AFTER DUODENOJEJUNOSTOMY IN AN EXPERIMENTAL MODEL OF TYPE 2 DIABETES MELLITUS

2016 ◽  
Vol 29 (suppl 1) ◽  
pp. 3-7 ◽  
Author(s):  
Cacio Ricardo WIETZYCOSKI ◽  
João Caetano Dallegrave MARCHESINI ◽  
Sultan AL-THEMYAT ◽  
Fabiola Shons MEYER ◽  
Manoel Roberto Maciel TRINDADE
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Control Group ◽  
Oral Glucose ◽  
Surgical Group

ABSTRACT Background: Type 2 Diabetes Mellitus is a multifactorial syndrome with severe complications. Oxidative stress is accepted as a causal factor of chronic complications Aim: To demonstrate alterations in oxidative stress after metabolic surgery. Methods: Twenty-four 2-day-old Wistar rats were used. In 16, Type 2 Diabetes Mellitus was induced by 100 mg/kg streptozotocin injection. The development of diabetes was confirmed after 10 weeks using an oral glucose tolerance test. Eight diabetic rats composed the diabetic surgical group; the remaining eight composed the diabetic group. Eight animals in which diabetes was not induced formed the clinical control group. The Marchesini technique was used in the diabetic surgical group. After 90 days, the rats were sacrificed, and the oxidative stress markers were measured. Results: Thiobarbituric acid reactive substances, superoxide dismutase and catalase were significantly reduced in the diabetic surgical group compared to the diabetic group. Conclusion: The duodenojejunostomy was effective in controlling the exacerbated oxidative stress present in diabetic rats.

scholarly journals Insulin Resistance in Osteoarthritis: Similar Mechanisms to Type 2 Diabetes Mellitus

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Elena V Tchetina ◽  
Galina A Markova ◽  
Eugeniya P Sharapova
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
The Body ◽  
Whole Body ◽  
Insulin Resistant ◽  
Resistant State ◽  
Insulin Resistant State

Osteoarthritis (OA) and type 2 diabetes mellitus (T2D) are two of the most widespread chronic diseases. OA and T2D have common epidemiologic traits, are considered heterogenic multifactorial pathologies that develop through the interaction of genetic and environmental factors, and have common risk factors. In addition, both of these diseases often manifest in a single patient. Despite differences in clinical manifestations, both diseases are characterized by disturbances in cellular metabolism and by an insulin-resistant state primarily associated with the production and utilization of energy. However, currently, the primary cause of OA development and progression is not clear. In addition, although OA is manifested as a joint disease, evidence has accumulated that it affects the whole body. As pathological insulin resistance is viewed as a driving force of T2D development, now, we present evidence that the molecular and cellular metabolic disturbances associated with OA are linked to an insulin-resistant state similar to T2D. Moreover, the alterations in cellular energy requirements associated with insulin resistance could affect many metabolic changes in the body that eventually result in pathology and could serve as a unified mechanism that also functions in many metabolic diseases. However, these issues have not been comprehensively described. Therefore, here, we discuss the basic molecular mechanisms underlying the pathological processes associated with the development of insulin resistance; the major inducers, regulators, and metabolic consequences of insulin resistance; and instruments for controlling insulin resistance as a new approach to therapy.

scholarly journals Changes in microvascular density differentiate metabolic health outcomes in monkeys with prior radiation exposure and subsequent skeletal muscle ECM remodeling

2017 ◽  
Vol 313 (3) ◽  
pp. R290-R297 ◽  
Author(s):  
K. M. Fanning ◽  
B. Pfisterer ◽  
A. T. Davis ◽  
T. D. Presley ◽  
I. M. Williams ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Radiation Exposure ◽  
Microvascular Density ◽  
Whole Body ◽  
Ecm Remodeling

Radiation exposure accelerates the onset of age-related diseases such as diabetes, cardiovascular disease, and neoplasia and, thus, lends insight into in vivo mechanisms common to these disorders. Fibrosis and extracellular matrix (ECM) remodeling, which occur with aging and overnutrition and following irradiation, are risk factors for development of type 2 diabetes mellitus. We previously demonstrated an increased incidence of skeletal muscle insulin resistance and type 2 diabetes mellitus in monkeys that had been exposed to whole body irradiation 5–9 yr prior. We hypothesized that irradiation-induced fibrosis alters muscle architecture, predisposing irradiated animals to insulin resistance and overt diabetes. Rhesus macaques ( Macaca mulatta, n = 7–8/group) grouped as nonirradiated age-matched controls (Non-Rad-CTL), irradiated nondiabetic monkeys (Rad-CTL), and irradiated monkeys that subsequently developed diabetes (Rad-DM) were compared. Prior radiation exposure resulted in persistent skeletal muscle ECM changes, including a relative overabundance of collagen IV and a trend toward increased transforming growth factor-β1. Preservation of microvascular markers differentiated the irradiated diabetic and nondiabetic groups. Microvascular density and plasma nitrate and heat shock protein 90 levels were lower in Rad-DM than Rad-CTL. These results are consistent with a protective effect of abundant microvasculature in maintaining glycemic control within radiation-induced fibrotic muscle.

scholarly journals CORRELATION BETWEEN APOB100/APOA1 RATIO AND INSULIN RESISTANCE IN TYPE 2 DIABETES MELLITUS

2019 ◽  
pp. 79-83
Author(s):  
SUCHETHA KUMARI N ◽  
SHILPA S SHETTY
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Density Lipoprotein ◽  
Diabetic Group ◽  
Study Results ◽  
Study Population ◽  
Lipid Abnormalities

Objective: Various lipid abnormalities are associated with Type 2 diabetes, thereby increasing the risk of cardiovascular disease and metabolic syndrome. The objective of the study is to correlate apolipoprotein ratio with insulin resistance (IR) to understand its role in Type 2 diabetes mellitus. Methods: The study population included 416 subjects of which 197 were non-diabetic and remaining 219 were non-diabetic and served as control subjects. Body mass index was calculated. Fasting plasma glucose, insulin, glycated hemoglobin levels, total cholesterol, triglyceride and high-density lipoprotein, ApoA-1, and ApoB-100 were measured using commercially available kits. Statistical analysis was performed with SPSS for Windows 16.0. Significance was defined as p<0.05. Results: Apolipoprotein A-1 levels were lower in the diabetic group whereas apolipoprotein B-100 levels, apolipoprotein ratios were higher in the diabetic group. ApoB100 and apolipoportein ratio showed a positive correlation with IR. Conclusions: The study results indicate that apolipoprotein B100/ApoA-1 ratio can act as a strong biomarker for IR.

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