scholarly journals Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Tadashi Okamura ◽  
Xiang Yuan Pei ◽  
Ichiro Miyoshi ◽  
Yukiko Shimizu ◽  
Rieko Takanashi-Yanobu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Mass ◽  
Spontaneous Diabetes ◽  
Tubular Epithelial Cell ◽  
The Body ◽  
Male Rats ◽  
Phenotypic Characterization ◽  
Dependent Manner ◽  
Long Evans

Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA) rat derived from Long-Evans (LE) strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction ofβ-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus.

scholarly journals Characterization of Novel Nonobese Type 2 Diabetes Rat Model with Enlarged Kidneys

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ayaka Domon ◽  
Kentaro Katayama ◽  
Yuki Tochigi ◽  
Hiroetsu Suzuki
Keyword(s):  
Type 2 Diabetes ◽  
Rat Model ◽  
Inflammatory Cells ◽  
The Body ◽  
Female Rats ◽  
Male Rats ◽  
Oral Glucose ◽  
Renal Tubules ◽  
Age Related

A variety of animal models of diabetes mellitus (DM) are required to study the genetics and pathophysiology of DM. We established a novel rat strain showing nonobese type 2 diabetes with enlarged kidneys from the LEA.PET-pet congenic strain and named it Diabetes with Enlarged Kidney (DEK). The body growth of DEK affected rats was similar to that of normal rats before the development of DM but was attenuated with the deterioration of DM. There was a marked difference in the etiology of DEK by gender: DM phenotypes including polyuria, polydipsia, and hyperglycemia (nonfasting blood glucose over 300 mg/dl) were found in male rats aged over 10 weeks but not in female rats. The cumulative incidence of DM in DEK males at the age of 30 weeks was 44.8%. Oral glucose tolerance tests showed glucose intolerance and decreased insulin secretion in response to glucose loading in affected males, features which were exacerbated with age. Affected males exhibited disorganized architecture of pancreatic islets, decreased numbers of β cells, and markedly decreased expression of insulin, despite no pathological findings of hemorrhage or infiltration of inflammatory cells in the pancreatic islet. Age-related islet fibrosis appeared similar in normal and affected males. Affected males also showed enlarged kidneys with dilation of renal tubules in both the cortex and medulla, but no obvious glomerular lesions typical of diabetic nephropathy (DN) at the age of 30 weeks. Plasma levels of urea nitrogen and creatinine were normal, but hypoalbuminemia was detected. These pathophysiological features in affected males indicated that their renal function was almost maintained despite severe DM. Taken together, these findings indicate that the affected males of the DEK strain are a novel nonobese type 2 diabetes rat model useful for studying the mechanisms underlying β cell loss and identifying genetic factors protective against DN.

scholarly journals Quercetin improves myocardial redox status in rats with type 2 diabetes

2021 ◽  
Vol 55 (3) ◽  
pp. 142-152
Author(s):  
Nataliia I. Gorbenko ◽  
Oleksii Yu. Borikov ◽  
Tetiana V. Kiprych ◽  
Olha V. Ivanova ◽  
Kateryna V. Taran ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Free Radical Oxidation ◽  
Redox Status ◽  
Diabetic Rats ◽  
The Body ◽  
Dependent Manner ◽  
Citrate Buffer ◽  
Radical Oxidation

Abstract Objective. Emerging data indicate that oxidative stress is closely associated with the pathogenesis of cardiovascular disease in type 2 diabetes mellitus (T2DM). The present study aimed to assess the effect of the most abundant flavonoid in the human diet quercetin (Q) on the myocardial redox status in rats with T2DM. Methods. T2DM was induced in male Wistar rats by a high caloric diet (for 14 weeks) and two streptozotocin (25 mg/kg b.w.) injections applied in four weeks of the diet, once a week for two weeks. The Q was administered intragastrically by gavage in a dose of 10 or 50 mg/kg of the body weight for 8 weeks starting from the 8th day after the last streptozotocin injection. The control rats received citrate buffer and seven days after the last STZ injection, basal glucose levels were measured in all animals. Results. Administration of Q increased insulin sensitivity in diabetic rats with more pronounced effect at a dose of 50 mg/kg b.w. The Q also decreased free radical oxidation in the heart mitochondria of diabetic animals, thus limiting the formation of advanced oxidation protein products in a dose-dependent manner and normalized the activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, glutathione reductase) in cardiac mitochondria independently of the dose used. In addition, the Q in both doses prevented the development of oxidative stress in the T2DM rats cardiomyocytes by reducing NADPH oxidase and xanthine oxidase activities. Conclusions. The findings demonstrate that Q in both doses 10 mg/kg and 50 mg/kg can protect from the development of oxidative stress in cardiomyocytes in the diabetic rats. The present data indicate that the use of Q may contribute to the amelioration of cardiovascular risk in patients with T2DM.

scholarly journals Early-Life Origins of Type 2 Diabetes: Fetal Programming of the Beta-Cell Mass

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Bernard Portha ◽  
Audrey Chavey ◽  
Jamileh Movassat
Keyword(s):  
Type 2 Diabetes ◽  
Gestational Diabetes ◽  
Beta Cell ◽  
Cell Mass ◽  
Spontaneous Diabetes ◽  
Metabolic Stress ◽  
Beta Cell Mass ◽  
Metabolic Disturbances ◽  
Obesity Hypertension

A substantial body of evidence suggests that an abnormal intrauterine milieu elicited by maternal metabolic disturbances as diverse as undernutrition, placental insufficiency, diabetes or obesity, may program susceptibility in the fetus to later develop chronic degenerative diseases, such as obesity, hypertension, cardiovascular diseases and diabetes. This paper examines the developmental programming of glucose intolerance/diabetes by disturbed intrauterine metabolic condition experimentally obtained in various rodent models of maternal protein restriction, caloric restriction, overnutrition or diabetes, with a focus on the alteration of the developing beta-cell mass. In most of the cases, whatever the type of initial maternal metabolic stress, the beta-cell adaptive growth which normally occurs during gestation, does not take place in the pregnant offspring and this results in the development of gestational diabetes. Therefore gestational diabetes turns to be the ultimate insult targeting the offspring beta-cell mass and propagates diabetes risk to the next generation again. The aetiology and the transmission of spontaneous diabetes as encountered in the GK/Par rat model of type 2 diabetes, are discussed in such a perspective. This review also discusses the non-genomic mechanisms involved in the installation of the programmed effect as well as in its intergenerational transmission.

scholarly journals Cholecystokinin Suppresses β-Cell Apoptosis, Including in Human Islets in a Transplant Model

2021 ◽  
Author(s):  
Hung Tae Kim ◽  
Arnaldo H. de Souza ◽  
Heidi Umhoefer ◽  
JeeYoung Han ◽  
Lucille Anzia ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Survival ◽  
Cell Apoptosis ◽  
Cell Mass ◽  
Human Islets ◽  
Dependent Manner ◽  
Pancreatic Β Cell ◽  
Β Cell

AbstractLoss of functional pancreatic β-cell mass and increased β-cell apoptosis are fundamental to the pathophysiology of both type 1 and type 2 diabetes. Pancreatic islet transplantation has the potential to cure type 1 diabetes but is often ineffective due to the death of the islet graft within the first few years after transplant. Therapeutic strategies to directly target pancreatic β-cell survival are needed to prevent and treat diabetes and to improve islet transplant outcomes. Reducing β-cell apoptosis is also a therapeutic strategy for type 2 diabetes. Cholecystokinin (CCK) is a peptide hormone typically produced in the gut after food intake, with positive effects on obesity and glucose metabolism in mouse models and human subjects. We have previously shown that pancreatic islets also produce CCK. The production of CCK within the islet promotes β-cell survival in rodent models of diabetes and aging. Now, we demonstrate a direct effect of CCK to reduce cytokine-mediated apoptosis in a β-cell line and in isolated mouse islets in a receptor-dependent manner. However, whether CCK can protect human β-cells was previously unknown. Here, we report that CCK can also reduce cytokine-mediated apoptosis in isolated human islets and CCK treatment in vivo decreases β-cell apoptosis in human islets transplanted into the kidney capsule of diabetic NOD/SCID mice. Collectively, these data identify CCK as a novel therapy that can directly promote β-cell survival in human islets and has therapeutic potential to preserve β-cell mass in diabetes and as an adjunct therapy after transplant.One Sentence SummaryCholecystokinin ameliorates pancreatic β-cell death under models of stress and after transplant of human islets.

Vitamin D Supplementation and Serum Levels of Magne-sium and Selenium in Type 2 Diabetes Mellitus Patients: Gender Dimorphic Changes

2014 ◽  
Vol 84 (1-2) ◽  
pp. 27-34 ◽  
Author(s):  
Nasser M. Al-Daghri ◽  
Khalid M. Alkharfy ◽  
Nasiruddin Khan ◽  
Hanan A. Alfawaz ◽  
Abdulrahman S. Al-Ajlan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Type 2 Diabetes Mellitus ◽  
Serum Levels ◽  
Vitamin D Supplementation ◽  
Serum Selenium ◽  
Dependent Manner

The aim of our study was to evaluate the effects of vitamin D supplementation on circulating levels of magnesium and selenium in patients with type 2 diabetes mellitus (T2DM). A total of 126 adult Saudi patients (55 men and 71 women, mean age 53.6 ± 10.7 years) with controlled T2DM were randomly recruited for the study. All subjects were given vitamin D3 tablets (2000 IU/day) for six months. Follow-up mean concentrations of serum 25-hydroxyvitamin D [25-(OH) vitamin D] significantly increased in both men (34.1 ± 12.4 to 57.8 ± 17.0 nmol/L) and women (35.7 ± 13.5 to 60.1 ± 18.5 nmol/L, p < 0.001), while levels of parathyroid hormone (PTH) decreased significantly in both men (1.6 ± 0.17 to 0.96 ± 0.10 pmol/L, p = 0.003) and women (1.6 ± 0.17 to 1.0 ± 0.14 pmol/L, p = 0.02). In addition, there was a significant increase in serum levels of selenium and magnesium in men and women (p-values < 0.001 and 0.04, respectively) after follow-up. In women, a significant correlation was observed between delta change (variables at six months-variable at baseline) of serum magnesium versus high-density lipoprotein (HDL)-cholesterol (r = 0.36, p = 0.006) and fasting glucose (r = - 0.33, p = 0.01). In men, there was a significant correlation between serum selenium and triglycerides (r = 0.32, p = 0.04). Vitamin D supplementation improves serum concentrations of magnesium and selenium in a gender-dependent manner, which in turn could affect several cardiometabolic parameters such as glucose and lipids.

Serum Ferritin Status of Patients with Type 2 DM Attending OPD of BIRDEM General Hospital

2020 ◽  
Vol 11 (1) ◽  
pp. 7-10
Author(s):  
Khadiza Begum ◽  
Fahmida Islam ◽  
Farjana Aktar ◽  
Murshida Aziz ◽  
Tohfa E Ayub Tahiya
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Serum Ferritin ◽  
Study Groups ◽  
Acute Phase Reactant ◽  
The Body ◽  
Iron Stores ◽  
Normal Healthy Individual ◽  
Diabetes Patients

Background: In recent times much is talked about of serum ferritin, an acute phase reactant a marker of iron stores in the body and its association with diabetes mellitus. Studies implicate that increased body iron stores and subclinical hemochromatosis has been associated with the development of glucose intolerance, type 2 diabetes and its micro as well as macrovascular complications. Material & Methods: This study was carried out to examine and to observe for any relationship between serum ferritin with Type 2 diabetes mellitus. Our study populations were included 163. Among them 81 type 2 diabetes patients as a case (M=49,F=32, mean 44.68 age in years)and 82 normal healthy individual as a control ( M=35, F=47 , mean 34.71 in years). Results: Majority were healthy outpatients who had come for regular checkup and were matched with controls. Serum ferritin and FBS were estimated and other investigations. Results showed that although Serum ferritin was in the normal range value it was increased in type 2 diabetes patients than in controls and was statistically significant, we did get a positive correlation with duration of diabetes. It can be concluded that there were positive associations between serum ferritin and FBG, age, sex among study groups. Conclusion: In conclusion our study shows that there is significant correlation between increased serum ferritin in diabetes compared to individuals with normal blood sugars in this part and hyper ferritinemia may be one of the causes for development of insulin resistance before overt diabetes. Anwer Khan Modern Medical College Journal Vol. 11, No. 1: Jan 2020, P 7-10

scholarly journals Reduction of estimated fluid volumes following initiation of empagliflozin in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the placebo-controlled, randomized EMBLEM trial

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Atsushi Tanaka ◽  
Michio Shimabukuro ◽  
Hiroki Teragawa ◽  
Yosuke Okada ◽  
Toshinari Takamura ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Repeated Measures ◽  
Medical Information ◽  
Controlled Trial ◽  
Extracellular Volume ◽  
Cardiovascular Outcomes ◽  
Fluid Volume ◽  
The Body

Abstract Backgrounds/Aim Sodium glucose co-transporter 2 inhibitors promote osmotic/natriuretic diuresis and reduce excess fluid volume, and this improves cardiovascular outcomes, including hospitalization for heart failure. We sought to assess the effect of empagliflozin on estimated fluid volumes in patients with type 2 diabetes and cardiovascular disease (CVD). Methods The study was a post-hoc analysis of the EMBLEM trial (UMIN000024502), an investigator-initiated, multi-center, placebo-controlled, double-blinded, randomized-controlled trial designed primarily to evaluate the effect of 24 weeks of empagliflozin treatment on vascular endothelial function in patients with type 2 diabetes and established CVD. The analysis compared serial changes between empagliflozin (10 mg once daily, n = 52) and placebo (n = 53) in estimated plasma volume (ePV), calculated by the Straus formula and estimated the extracellular volume (eEV), determined by the body surface area, measured at baseline and 4, 12, and 24 weeks after initiation of treatment. Correlations were examined between the changes from baseline to week 24 in each estimated fluid volume parameter and several clinical variables of interest, including N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration. Results In an analysis using mixed-effects models for repeated measures, relative to placebo empagliflozin reduced ePV by − 2.23% (95% CI − 5.72 to 1.25) at week 4, − 8.07% (− 12.76 to − 3.37) at week 12, and − 5.60% (− 9.87 to − 1.32) at week 24; eEV by − 70.3 mL (95% CI − 136.8 to − 3.8) at week 4, − 135.9 mL (− 209.6 to − 62.3) at week 12, and − 144.4 mL (− 226.3 to − 62.4) at week 24. The effect of empagliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in log-transformed NT-proBNP was positively correlated with change in ePV (r = 0.351, p = 0.015), but not with change in eEV. Conclusions Our data demonstrated that initiation of empagliflozin treatment substantially reduced estimated fluid volume parameters in patients with type 2 diabetes and CVD, and that this effect was maintained for 24 weeks. Given the early beneficial effect of empagliflozin on cardiovascular outcomes seen in similar patient populations, our findings provide an important insight into the key mechanisms underlying the clinical benefit of the drug. Trial registration University Medical Information Network Clinical Trial Registry, number 000024502

scholarly journals Reduced beta cell number rather than size is a major contributor to beta cell loss in type 2 diabetes

Diabetologia ◽  
2021 ◽  
Author(s):  
Hironobu Sasaki ◽  
Yoshifumi Saisho ◽  
Jun Inaishi ◽  
Yuusuke Watanabe ◽  
Tami Tsuchiya ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Cell Size ◽  
Cell Mass ◽  
Cell Number ◽  
Relative Reduction ◽  
Major Contributor ◽  
Islet Morphology ◽  
The Impact

Abstract Aims/hypothesis Type 2 diabetes is characterised by reduced beta cell mass (BCM). However, it remains uncertain whether the reduction in BCM in type 2 diabetes is due to a decrease in size or number of beta cells. Our aim was to examine the impact of beta cell size and number on islet morphology in humans with and without type 2 diabetes. Methods Pancreas samples were obtained from 64 Japanese adults with (n = 26) and without (n = 38) type 2 diabetes who underwent pancreatectomy. Using pancreatic tissues stained for insulin, we estimated beta cell size based on beta cell diameter. Beta cell number was estimated from the product of fractional beta cell area and pancreas volume divided by beta cell size. The associations of beta cell size and number with islet morphology and metabolic status were examined. Results Both beta cell size (548.7 ± 58.5 vs 606.7 ± 65.0 μm3, p < 0.01) and number (5.10 × 108 ± 2.35 × 108 vs 8.16 × 108 ± 4.27 × 108, p < 0.01) were decreased in participants with type 2 diabetes compared with those without diabetes, with the relative reduction in beta cell number (37%) being greater than for beta cell size (10%). Beta cell number but not size was positively correlated with BCM in participants with and without type 2 diabetes (r = 0.97 and r = 0.98, both p < 0.01) and negatively correlated with HbA1c (r = −0.45, p < 0.01). Conclusions/interpretation Both beta cell size and number were reduced in participants with type 2 diabetes, with the relative reduction in beta cell number being greater. Decrease in beta cell number appears to be a major contributor to reduced BCM in type 2 diabetes. Graphical abstract

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