Effects of Habitual Perilla (Shiso) Tea Drinking on the Incidence of Diabetes Mellitus in Spontaneously Diabetic Trii (SDT)Rats

The anti-diabetic effect of perilla (shiso) tea was evaluated in vivo. When shiso tea was given to model rats that spontaneously developed diabetes mellitus (DM), the development of DM was decelerated. In oral glucose tolerance tests, the disappearance of blood glucose in rats administered shiso tea was reinforced. These results suggest that habitual drinking of shiso tea is effective in preventing the onset of diabetes.     

Effects of the aqueous extract of white tea (Camellia sinensis) in a streptozotocin-induced diabetes model of rats

White tea (WT) is very similar to green tea (GT) but it is exceptionally prepared only from the buds and young tea leaves of Camelia sinensis plant while GT is prepared from the matured tea leaves. The present study was investigated to examine the effects of a 0.5% aqueous extract of WT in a streptozotocin-induced diabetes model of rats. Six-week-old male Sprague-Dawley rats were divided into 3 groups of 6 animals in each group namely: normal control (NC), diabetic control (DBC) and diabetic white tea (DWT). Diabetes was induced by an intraperitoneal injection of streptozotocin (65 mg/kg BW) in DBC and DWT groups except the NC group. After 4 weeks feeding of 0.5% aqueous extracts of WT, the drink intake was significantly (P < 0.05) increased in the DWT group compared to the DBC and NC groups. Blood glucose concentrations were significantly decreased and glucose tolerance ability was significantly improved in the DWT group compared to the DBC group. Liver weight and liver glycogen were significantly increased and serum total cholesterol and LDL-cholesterol were significantly decreased in the DWT group compared to the DBC group. The food intake, body weight gain, serum insulin and fructosamine concentrations were not influenced by the consumption of WT. Data of this study suggest that the 0.5% aqueous extract of WT is effective to reduce most of the diabetes associated abnormalities in a steptozotocin-induced diabetes model of rats.     

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

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 beta-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 beta-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 beta-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.     

有氧运动与饮食控制对2型糖尿病大鼠肝chemerin及其受体CMKLR1的影响

目的：研究4周有氧运动与饮食控制对2型糖尿病（DM）大鼠肝chemerin及其受体趋化因子样受体1（CMKLR1）的影响及其在改善糖脂代谢中的影响。方法：50只雄性SD大鼠随机分为正常对照组（Con,n=6）和糖尿病造模组（n=44）。采用高脂高糖饲料联合小剂量链脲佐菌素（STZ）（30 mg/kg）的方法制备2型糖尿病模型大鼠。造模成功的DM大鼠随机分为4组（n=6）：糖尿病对照组（DM）、糖尿病运动组（EDM）、改喂普通饲料的糖尿病饮食控制组（NDM）和糖尿病运动+饮食控制组（ENDM）。运动组大鼠进行为期4周中等强度跑台有氧运动,每周运动6 d。采用罗氏血糖仪检测大鼠空腹血糖（FBG）,全自动生化分析仪检测大鼠血清总胆固醇（TC）、甘油三酯（TG）和低密度脂蛋白（LDL）水平,real time PCR和Western blot分别检测大鼠肝chemerin、CMKLR1的mRNA和蛋白水平。结果：DM大鼠FBG和血清TC、TG、LDL水平显著升高的同时,肝chemerin和CMKLR1的mRNA和蛋白水平显著增加;4周有氧运动和/或饮食控制显著降低EDM、NDM和ENDM组FBG和血清TC、TG、LDL的同时,显著降低这3组大鼠的肝chemerin蛋白水平,其中ENDM组降低最显著（P<0.01）;NDM和ENDM组大鼠的肝CMKLR1蛋白水平升高（P<0.01）。结论：4周有氧运动和/或饮食控制降低2型糖尿病大鼠的肝chemerin蛋白水平、增加CMKLR1蛋白水平,这可能与其改善糖尿病大鼠的糖脂代谢有关。     

Enhanced autophagy plays a cardinal role in mitochondrial dysfunction in type 2 diabetic Goto-Kakizaki (GK) rats: ameliorating effects of (-)-epigallocatechin-3-gallate

Oxidative stress and mitochondrial dysfunction are known to play important roles in type 2 diabetes mellitus (T2DM) and insulin resistance. However, the pathology of T2DM remains complicated; in particular, the mechanisms of mitochondrial dysfunction in skeletal muscle and other insulin-sensitive tissues are as yet unclear. In the present study, we investigated the underlying mechanisms of oxidative stress and mitochondrial dysfunction by focusing on mitochondrial dynamics, including mitochondrial biogenesis and autophagy, in skeletal muscle of a nonobese diabetic animal model--the Goto-Kakizaki (GK) rat. The results showed that GK rats exhibited impaired glucose metabolism, increased oxidative stress and decreased mitochondrial function. These dysfunctions were found to be associated with induction of LC3B, Beclin1 and DRP1 (key molecules mediating the autophagy pathway), while they appeared not to affect the mitochondrial biogenesis pathway. In addition, (-)-epigallocatechin-3-gallate (EGCG) was tested as a potential autophagy-targeting nutrient, and we found that EGCG treatment improved glucose tolerance and glucose homeostasis in GK rats, and reduced oxidative stress and mitochondrial dysfunction in skeletal muscle. Amelioration of excessive muscle autophagy in GK rats through the down-regulation of the ROS-ERK/JNK-p53 pathway leads to improvement of glucose metabolism, reduction of oxidative stress and inhibition of mitochondrial loss and dysfunction. These results suggest (a) that hyperglycemia-associated oxidative stress may induce autophagy through up-regulation of the ROS-ERK/JNK-p53 pathway, which may contribute to mitochondrial loss in soleus muscle of diabetic GK rats, and (b) that EGCG may be a potential autophagy regulator useful in treatment of insulin resistance.     

Deterioration of Bone Quality by Streptozotocin (STZ)-Induced Type 2 Diabetes Mellitus in Rats

Patients with diabetes mellitus (DM) have various skeletal disorders and bone quality can be impaired in DM leading to fractures. Wistar albino male rats (270?C300?g; n?=?16) were assigned randomly to nondiabetic and diabetic rats (single dose intravenous injection of 45?mg/kg streptozotocin). All rats in each group were perpetuated for 8?weeks, and blood glucose levels as well as body weights were measured once weekly. Biomechanical measurements were performed at the mid-diaphysis of the left femur with tensile test. Extrinsic and intrinsic properties were measured or calculated. Bone mineral density (BMD) was also evaluated and measured by dual-energy X-ray absorptiometry. Cross-sectional area of the femoral shaft was evaluated by computerized tomography. Blood glucose levels in diabetic rats were significantly increased compared to that of the nondiabetic rats, while the body and femur weights were decreased (P?<?0.05). In respect to the BMD, cross-sectional area and femur length, there were no statistically significant differences between the nondiabetic and diabetic rats (P?>?0.05). The maximum load, ultimate stress, and toughness endpoints in diabetic rats were significantly decreased compared to that of the nondiabetics (P?<?0.05). There were no statistically significant differences between the nondiabetic and diabetic rats with regard to the displacement and stiffness (P?>?0.05). Femurs of diabetic rats had less absorbed energy than that in nondiabetics (P?<?0.05). Ultimate strain was lower in diabetic rats than that in nondiabetics, while the elastic modulus was higher (P?>?0.05). The bone quality of rats is decreased by streptozotocin-induced type 2 diabetes mellitus.     

Chronic alcohol consumption,type 2 diabetes mellitus,insulin-like growth factor-I (IGF-I), and growth hormone (GH) in ethanol-treated diabetic rats

Aims

Alcohol has deleterious influences on glucose metabolism which may contribute to the development of type 2 diabetes mellitus (T2DM). Insulin-like growth factor I (IGF-I) and growth hormone (GH), which interact with insulin to modulate metabolic control, have been shown to be related to impaired glucose tolerance. This study was conducted to assess the possibility that altered circulating IGF-I and GH levels contribute to the exacerbation of T2DM by alcohol use in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats.

Main method

OLETF rats were pair-fed a Lieber-DeCarli Regular Ethanol diet and LETO rats were pair-fed a control diet for 6 weeks. At 6 weeks, an Intraperitoneal Glucose Tolerance Test (IP-GTT) was performed and IGF-I and GH levels were evaluated.

Key findings

Prior to an IP-GTT, OLETF-Ethanol (O-E) group had significantly a decrease in the mean glucose levels compared to OLETF-Control (O-C) group. At 120 min post IP-GTT, the O-E group had significantly an increase in the mean glucose levels compared to O-C group. The serum IGF-I levels were significantly lower and the serum GH levels were significantly higher in the O-E group than in L-C group.

Significance

These results suggest that IGF-I and GH are prominent in defining the risk and development of T2DM, and may be adversely affected by heavy alcohol use, possibly mediating its diabetogenic effects. Thus, the overall glucose intolerance in the setting of alcoholism may be attributable to inappropriate alteration of IGF-I and GH levels.     

Resveratrol, a red wine antioxidant, possesses an insulin-like effect in streptozotocin-induced diabetic rats

Aberrant energy metabolism is one characteristic of diabetes mellitus (DM). Two types of DM have been identified, type 1 and type 2. Most of type 2 DM patients eventually become insulin dependent because insulin secretion by the islets of Langerhans becomes exhausted. In the present study, we show that resveratrol (3,5,4'-trihydroxylstilbene) possesses hypoglycemic and hypolipidemic effects in streptozotocin-induced DM (STZ-DM) rats. In resveratrol-treated STZ-DM rats, the plasma glucose concentration on day 14 was reduced by 25.3 +/- 4.2%, and the triglyceride concentration was reduced by 50.2 +/- 3.2% compared with the vehicle-treated rats. In STZ-nicotinamide DM rats, the plasma glucose concentration on day 14 was reduced by 20.3 +/- 4.2%, and the triglyceride concentration was reduced by 33.3 +/- 2.2% compared with the vehicle-treated rats. Resveratrol administration ameliorates common DM symptoms, such as body weight loss, polyphagia, and polydipsia. In STZ-nicotinamide DM rats, resveratrol administration significantly decreased insulin secretion and delayed the onset of insulin resistance. Further studies showed that glucose uptake by hepatocytes, adipocytes, and skeletal muscle and hepatic glycogen synthesis were all stimulated by resveratrol treatment. Because the stimulation of glucose uptake was not attenuated in the presence of an optimal amount of insulin in insulin-responsive cells, the antihyperglycemic effect of resveratrol appeared to act through a mechanism(s) different from that of insulin.     

Resveratrol increases stem cell function in the treatment of damaged pancreas

Pancreatic damage results in insufficient insulin secretion, leading to type 1 diabetes. Stem cell-based therapy has recently shown potential in the treatment of type 1 diabetes. Resveratrol supplementation has demonstrated a beneficial effect in treating diabetes. This study investigates if adipose-derived stem cells (ADSC), preconditioned with resveratrol, show better effects on experimental diabetic animals. Wistar rats were randomly divided into four groups including sham (normal rats), DM (diabetic rats induced by SZT injection), DM+ADSC (DM rats with receiving autologous ADSC transplantation) and DM+R-ADSC (DM rats receiving resveratrol preconditioned ADSC). The experimental results show that SZT induced pancreatic damage (DM group), including reduction of islet size, fibrosis pathway activation, survival signaling suppression, and apoptotic pathway expression, lead to serum glucose elevation. Autologous ADSC (DM+ADSC group) transplantation shows improvement in the above observations in DM rats. Furthermore, ADSC precondition with resveratrol (DM+R-ADSC group) reveals significant improvement in the above pathological observations over both DM and DM+ADSC groups. We found that ADSC precondition with resveratrol increases the survival marker p-Akt expression, leading to enhanced ADSC viability. This study suggests that ADSC precondition with resveratrol shows potential in the treatment of patients with type 1 DM.     

Postprandial Hypertriglyceridemia Predicts Development of Insulin Resistance Glucose Intolerance and Type 2 Diabetes

Insulin resistance (IR) and type 2 diabetes mellitus (T2DM) have been found to be associated with postprandial hypertriglyceridemia (PPHTg). However, whether PPHTg can cause IR and diabetes is not clear. We therefore investigated the role of PPHTg in development of T2DM in rat model of T2DM. 96 male Wistar rats were randomized into four groups (24 rats each). Control Group A, high sucrose diet (HSD) Group B, HSD+Pioglitazone (10mg/kg/day) Group C and HSD+Atorvastatin (20mg/kg/day) Group D. Fat and glucose tolerance tests were done at regular intervals in all groups besides insulin and body weight measurement. At 26 weeks, low dose streptozotocin (15mg/kg,i.p.) was given to half of the rats. All rats were followed up till 48 weeks. PPHTg developed as early as week 2 in Group B and stabilized by week 14. Group B displayed highest PPHTg compared to other groups. Atorvastatin treatment (Group D) abolished PPHTg which became comparable to controls, pioglitazone treatment partially blunted PPHTg resulting in intermediate PPHTg. Group B with highest PPHTg showed highest subsequent IR, glucose intolerance (GI) and highest incidence of prediabetes at week 26 and diabetes at week 34 and 46 compared to other groups. Group D rats displayed lower IR, GI, low incidence of prediabetes and diabetes at these time points compared to Groups B and C. ROC analysis showed that triglyceride area under the curve of each time point significantly predicts the risk of diabetes. Present study provides the evidence that PPHTg predicts the development of IR, GI and T2DM in rat model of diet induced T2DM.     

Glucose sensing by gut endocrine cells and activation of the vagal afferent pathway is impaired in a rodent model of type 2 diabetes mellitus

Glucose in the gut lumen activates gut endocrine cells to release 5-HT, glucagon-like peptide 1/2 (GLP-1/2), and glucose-dependent insulinotropic polypeptide (GIP), which act to change gastrointestinal function and regulate postprandial plasma glucose. There is evidence that both release and action of incretin hormones is reduced in type 2 diabetes (T2D). We measured cellular activation of enteroendocrine and enterochromaffin cells, enteric neurons, and vagal afferent neurons in response to intestinal glucose in a model of type 2 diabetes mellitus, the UCD-T2DM rat. Prediabetic (PD), recent-diabetic (RD, 2 wk postonset), and 3-mo diabetic (3MD) fasted UCD-T2DM rats were given an orogastric gavage of vehicle (water, 0.5 ml /100 g body wt) or glucose (330 μmol/100 g body wt); after 6 min tissue was removed and cellular activation was determined by immunohistochemistry for phosphorylated calcium calmodulin-dependent kinase II (pCaMKII). In PD rats, pCaMKII immunoreactivity was increased in duodenal 5-HT (P < 0.001), K (P < 0.01) and L (P < 0.01) cells in response to glucose; glucose-induced activation of all three cell types was significantly reduced in RD and 3MD compared with PD rats. Immunoreactivity for GLP-1, but not GIP, was significantly reduced in RD and 3MD compared with PD rats (P < 0.01). Administration of glucose significantly increased pCaMKII in enteric and vagal afferent neurons in PD rats; glucose-induced pCaMKII immunoreactivity was attenuated in enteric and vagal afferent neurons (P < 0.01, P < 0.001, respectively) in RD and 3MD. These data suggest that glucose sensing in enteroendocrine and enterochromaffin cells and activation of neural pathways is markedly impaired in UCD-T2DM rats.     

Transcutaneous Electrical Nerve Stimulation (TENS) Improves the Diabetic Cytopathy (DCP) via Up-Regulation of CGRP and cAMP

The objective of this study was to investigate the effects and mechanism of Transcutaneous Electrical Nerve Stimulation (TENS) on the diabetic cytopathy (DCP) in the diabetic bladder. A total of 45 rats were randomly divided into diabetes mellitus (DM)/TENS group (n = 15), DM group (n = 15) and control group (n = 15). The rats in the DM/TENS and TENS groups were electronically stimulated (stimulating parameters: intensity-31 V, frequency-31 Hz, and duration of stimulation of 15 min) for three weeks. Bladder histology, urodynamics and contractile responses to field stimulation and carbachol were determined. The expression of calcitonin gene-related peptide (CGRP) was analyzed by RT-PCR and Western blotting. The results showed that contractile responses of the DM rats were ameliorated after 3 weeks of TENS. Furthermore, TENS significantly increased bladder wet weight, volume threshold for micturition and reduced PVR, V% and cAMP content of the bladder. The mRNA and protein levels of CGRP in dorsal root ganglion (DRG) in the DM/TENS group were higher than those in the DM group. TENS also significantly up-regulated the cAMP content in the bladder body and base compared with diabetic rats. We conclude that TENS can significantly improve the urine contractility and ameliorate the feeling of bladder fullness in DM rats possibly via up-regulation of cAMP and CGRP in DRG.     

Disruption of circadian rhythms accelerates development of diabetes through pancreatic beta-cell loss and dysfunction

Type 2 diabetes mellitus (T2DM) is complex metabolic disease that arises as a consequence of interactions between genetic predisposition and environmental triggers. One recently described environmental trigger associated with development of T2DM is disturbance of circadian rhythms due to shift work, sleep loss, or nocturnal lifestyle. However, the underlying mechanisms behind this association are largely unknown. To address this, the authors examined the metabolic and physiological consequences of experimentally controlled circadian rhythm disruption in wild-type (WT) Sprague Dawley and diabetes-prone human islet amyloid polypeptide transgenic (HIP) rats: a validated model of T2DM. WT and HIP rats at 3 months of age were exposed to 10 weeks of either a normal light regimen (LD: 12:12-h light/dark) or experimental disruption in the light-dark cycle produced by either (1) 6-h advance of the light cycle every 3 days or (2) constant light protocol. Subsequently, blood glucose control, beta-cell function, beta-cell mass, turnover, and insulin sensitivity were examined. In WT rats, 10 weeks of experimental disruption of circadian rhythms failed to significantly alter fasting blood glucose levels, glucose-stimulated insulin secretion, beta-cell mass/turnover, or insulin sensitivity. In contrast, experimental disruption of circadian rhythms in diabetes-prone HIP rats led to accelerated development of diabetes. The mechanism subserving early-onset diabetes was due to accelerated loss of beta-cell function and loss of beta-cell mass attributed to increases in beta-cell apoptosis. Disruption of circadian rhythms may increase the risk of T2DM by accelerating the loss of beta-cell function and mass characteristic in T2DM.     

Reduction of post-prandial hyperglycemia by mulberry tea in type-2 diabetes patients

Aim

The dietary contents have a very important role in the management of metabolic syndrome along with type 2 diabetes mellitus (T2DM). Indian diet contains a large amount of carbohydrates that set off unpredictable blood sugar fluctuations and leads to increased risk of diabetic complications. The aim of the present study was to identify the effect of mulberry tea in the reduction of abnormally high postprandial blood glucose (PPG) levels in T2DM patients.

Methods

The study design was follow-up T2DM, 20 diabetic patients were given plain tea (control) and 28 diabetic patients were given mulberry tea (test subject) to measure the effect of mulberry tea on fasting blood glucose and PPG levels. Fasting blood glucose samples were collected after a standard breakfast. The PPG levels were recorded after the consumption of 70 ml tea along with 1 teaspoon of sugar after 90 min in all 48 patients.

Results

Fasting blood glucose levels in control and test group samples were found to be 178.55 ± 35.61 and 153.50 ± 48.10, respectively. After the consumption of plain tea and mulberry tea, the PPG values were recorded as 287.20 ± 56.37 and 210.21 ± 58.73, respectively. A highly significant (p < 0.001) change in the PPG level was observed in response to mulberry tea in all the test patients compared with control. Moreover, the effect size was also found to be very large (1.31).

Conclusion

Mulberry tea suppresses postprandial rise of blood glucose levels after 90 min of its consumption.     

Effects of a selective endothelin a receptor antagonist on the expressions of iNOS and eNOS in the heart of early streptozotocin-induced diabetic rats

Vascular tone is regulated through the actions of locally produced agents. Among the vasoconstrictors, the most potent agent is endothelin (ET), which exerts its vasoconstrictor actions principally through ET type A (ET(A)) receptors. Of the vasodilators, nitric oxide (NO) seems to be the most important contributor to the acute regulation of vascular tone. Vasculopathy is an important feature of diabetes mellitus (DM). Endogenous ET-mediated vasoconstrictor tone is augmented in diabetic states, and conflicting results persist concerning the NO system in diabetes. The present study investigated the expressions of inducible NO synthases (iNOS) and endothelial NOS (eNOS) in the heart of diabetic animals and the effects of a selective ET(A) receptor antagonist on these alterations. Type I diabetes was induced by intraperitoneal injection of streptozotocin (65 mg/kg) in Sprague-Dawley rats, while control (Con) rats received only citrate buffer. After 1 week, the streptozotocin-administered rats were randomly divided into two groups: the selective ET(A) receptor antagonist-administered group (DM+TA-0201, 1 mg/kg/day, by osmotic minipump for 2 weeks) and the DM+vehicle group (comprising the diabetic rats that received saline). The random blood glucose level was 405 +/- 103 mg/dl in DM animals, and this level was unchanged by ET antagonism. Body weight was more greatly decreased in DM rats than in Con rats, but the left ventricle to body weight ratio was increased in the DM group and was unaffected by ET antagonism. Protein expressions of eNOS and iNOS were assessed in the left ventricular tissues. eNOS expression was significantly increased in DM heart and was greatly inhibited by the treatment with ET antagonist. The expression of iNOS was also increased in early DM heart but was reversed by the ET antagonist. Thus, endothelin antagonism might be beneficial for DM heart by reversing the upregulated eNOS and iNOS expressions.     

(–)-Epigallocatechin-3-gallate attenuated myocardial mitochondrial dysfunction and autophagy in diabetic Goto–Kakizaki rats

Abstract

Type 2 diabetes mellitus (T2DM) is a risk factor for heart disease. However, the mechanisms of T2DM involvement in cardiac complications are still unclear. In the present study, we investigated mitochondria-related mechanisms underlying the pathogenesis of myocardial disorders in diabetic Goto–Kakizaki (GK) rats. We found that remarkable myocardial mitochondrial deficiency and dysfunction as well as oxidative stress occurred in the heart of GK rats. In addition, our results suggested that the loss of mitochondria was in response to elevated autophagy and upstream FoxO factors in diabetic myocardium. More importantly, (–)-epigallocatechin-3-gallate (EGCG), a polyphenol derived from green tea, successfully improved mitochondrial function and autophagy in the heart of GK rats. Our findings revealed that diabetes-associated myocardial mitochondrial deficiency and dysfunction was associated with enhanced autophagy in myocardium, and EGCG might be a potential agent in preventing and treating myocardial disorders involved in diabetes.     

Diabetes mellitus and its correlates in an Iranian adult population

The rising epidemic of diabetes imposes a substantial economic burden on the Middle East. Using baseline data from a population based cohort study, we aimed to identify the correlates of diabetes mellitus (DM) in a mainly rural population from Iran. Between 2004 and 2007, 50044 adults between 30 and 87 years old from Golestan Province located in Northeast Iran were enrolled in the Golestan Cohort Study. Demographic and health-related information was collected using questionnaires. Individuals' body sizes at ages 15 and 30 were assessed by validated pictograms ranging from 1 (very lean) to 7 in men and 9 in women. DM diagnosis was based on the self-report of a physician's diagnosis. The accuracy of self-reported DM was evaluated in a subcohort of 3811 individuals using fasting plasma glucose level and medical records. Poisson regression with robust variance estimator was used to estimate prevalence ratios (PR's). The prevalence of self-reported DM standardized to the national and world population was 5.7% and 6.2%, respectively. Self-reported DM had 61.5% sensitivity and 97.6% specificity. Socioeconomic status was inversely associated with DM prevalence. Green tea and opium consumption increased the prevalence of DM. Obesity at all ages and extreme leanness in childhood increased diabetes prevalence. Being obese throughout life doubled DM prevalence in women (PR: 2.1; 95% CI: 1.8, 2.4). These findings emphasize the importance of improving DM awareness, improving general living conditions, and early lifestyle modifications in diabetes prevention.     

Rare sugar d-psicose improves insulin sensitivity and glucose tolerance in type 2 diabetes Otsuka Long-Evans Tokushima Fatty (OLETF) rats

A rare sugar, d-psicose has progressively been evaluated as a unique metabolic regulator of glucose and lipid metabolism, and thus represents a promising compound for the treatment of type 2 diabetes mellitus (T2DM). The present study was undertaken to examine the underlying effector organs of d-psicose in lowering blood glucose and abdominal fat by exploiting a T2DM rat model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Rats were fed 5% d-psicose or 5% d-glucose supplemented in drinking water, and only water in the control for 13 weeks and the protective effects were compared. A non-diabetic Long-Evans Tokushima Otsuka (LETO), fed with water served as a counter control of OLETF. After 13 weeks feeding, d-psicose treatment significantly reduced the increase in body weight and abdominal fat mass. Oral glucose tolerance test (OGTT) showed the reduced blood glucose and insulin levels suggesting the improvement of insulin resistance in OLETF rats. Oil-red-O staining elucidated that d-psicose significantly reduced lipid accumulation in the liver. Immunohistochemical analysis showed d-psicose induced glucokinase translocation from nucleus to cytoplasm of the liver which enhances glucokinase activity and subsequent synthesis of glycogen in the liver. d-psicose also protected the pathological change of the β-cells of pancreatic islets. These data demonstrate that d-psicose controls blood glucose levels by reducing lipotoxicity in liver and by preserving pancreatic β-cell function.     

Induction of type-1 diabetes mellitus in laboratory rats by use of alloxan: route of administration, pitfalls, and insulin treatment

Uncertainties have existed regarding the systematic induction and management of drug-induced diabetes mellitus (DM). Issues have included the optimal route of administration of the drug, methods of reducing drug toxicosis and mortality, how to induce type-1 versus type-2 DM, and how to manage labile DM in rats. In attempting to induce type-1 DM in Sprague-Dawley rats, we classified hyperglycemic animals as having type-1 DM only if their post-treatment blood ketone concentration was high. We found that multiple doses of alloxan led to significantly higher mortality than did a single dose. A single high dose (200 mg/kg of body weight given intraperitoneally) was the best treatment and led to 70% incidence of type-1 DM and only 10% mortality. In contrast, intravenous administration of similar doses was toxic. Assiduous management of alloxan-induced DM is crucial to avoid severe hypoglycemia from massive insulin release and to avoid diabetic ketoacidosis. Frequent glucose monitoring and appropriate administration of carbohydrate and fluids is necessary during this stage. For long-term management, daily administration of long-acting insulin (glargine) appears to be safe and effective. Rapid-acting insulins reduce glucose concentration rapidly, and must be used with caution. If specific precautions are observed, intraperitoneal administration of high-dose alloxan to laboratory rats leads to a condition that closely resembles human type-1 DM.     

Metabolomic analysis and biochemical changes in the urine and serum of streptozotocin-induced normal- and obese-diabetic rats

Diabetes mellitus (DM) is a chronic disease that can affect metabolism of glucose and other metabolites. In this study, the normal- and obese-diabetic rats were compared to understand the diabetes disorders of type 1 and 2 diabetes mellitus. This was done by evaluating their urine metabolites using proton nuclear magnetic resonance (¹H NMR)-based metabolomics and comparing with controls at different time points, considering the induction periods of obesity and diabetes. The biochemical parameters of the serum were also investigated. The obese-diabetic model was developed by feeding the rats a high-fat diet and inducing diabetic conditions with a low dose of streptozotocin (STZ) (25 mg/kg bw). However, the normal rats were induced by a high dose of STZ (55 mg/kg bw). A partial least squares discriminant analysis (PLS-DA) model showed the biomarkers of both DM types compared to control. The synthesis and degradation of ketone bodies, tricarboxylic (TCA) cycles, and amino acid pathways were the ones most involved in the variation with the highest impact. The diabetic groups also exhibited a noticeable increase in the plasma glucose level and lipid profile disorders compared to the control. There was also an increase in the plasma cholesterol and low-density lipoprotein (LDL) levels and a decline in the high-density lipoprotein (HDL) of diabetic rats. The normal-diabetic rats exhibited the highest effect of all parameters compared to the obese-diabetic rats in the advancement of the DM period. This finding can build a platform to understand the metabolic and biochemical complications of both types of DM and can generate ideas for finding targeted drugs.