Advance in islet β cell development and regeneration

Islet β cells excrete insulin and play a crucial role in glucose homeostasis. Decreased β cell mass or/and β cell dysfunction are one of the fundamental characteristics of diabetes. The advance in understanding β cell development and regeneration provides new approaches to diabetes treatment. This review focuses on the molecular mechanism about β cell development and the sources for β cell regeneration.     

Effect of deoxycorticosterone acetate-salt-induced hypertension on diabetic peripheral neuropathy in alloxan-induced diabetic WBN/Kob rats

The relationship between hypertension and diabetic peripheral neuropathy (DPN) has recently been reported in clinical research, but it remains unclear whether hypertension is a risk factor for DPN. To investigate the effects of hypertension on DPN, we analyzed morphological features of peripheral nerves in diabetic rats with hypertension. Male WBN/Kob rats were divided into 2 groups: alloxan-induced diabetic rats with deoxycorticosterone acetate-salt (DOCA-salt) treatment (ADN group) and nondiabetic rats with DOCA-salt treatment (DN group). Sciatic, tibial (motor) and sural (sensory) nerves were subjected to qualitative and quantitative histomorphological analysis. Systolic blood pressure in the two groups exhibited a higher value (>140 mmHg), but there was no significant difference between the two groups. Endoneurial blood vessels in both groups presented endothelial hypertrophy and narrowing of the vascular lumen. Electron microscopically, duplication of basal lamina surrounding the endothelium and pericyte of the endoneurial vessels was observed, and this lesion appeared to be more frequent and severe in the ADN group than the DN group. Many nerve fibers of the ADN and DN groups showed an almost normal appearance, whereas morphometrical analysis of the tibial nerve showed a significant shift to smaller fiber and myelin sizes in the ADN group compared with DN group. In sural nerve, the fiber and axon-size significantly shifted to a smaller size in ADN group compared with the DN group. These results suggest that combined diabetes and hypertension could induce mild peripheral nerve lesions with vascular changes.     

Influence of obesity on first-phase insulin secretion in individuals with different glucose tolerance

AIM: To explore the influence of obesity on the first-phase insulin secretion in the individuals with different glucose tolerance. METHODS: Thirty-eight subjects with normal glucose tolerance without family history of diabetes (normal control,NC), 32 subjects with normal glucose tolerance (NGT) who were the first-degree relatives of type 2 diabetic patients, 67 patients with impaired glucose regulation (IGR) and 35 newly-diagnosed type 2 diabetic patients (T2DM) were enrolled in the study. The patients in the 4 groups were further divided into 2 subgroups: overweight/obesity and normal weight subgroups. All subjects received oral glucose-insulin release test (OG-IRT) and intravenous glucose tolerance test (IVGTT). Acute insulin response at 3~5 min (AIR3-5) was used to reflect first-phase insulin secretion,and insulin sensitivity index (ISI) was used to reflect insulin sensitivity. The influence of obesity on the islet β-cell function and insulin sensitivity in the individuals with different glucose tolerance was observed. RESULTS: The level of AIR3-5 in NC overweight/obesity subgroup was significantly higher than that in normal weight subgroup (P<0.05), while there was no significant difference between other subgroups (P>0.05). No significant difference in the level of ISI between the patients of IGR in overweight/obesity subgroup and normal weight subgroup was observed, while in the other 3 overweight/obesity subgroups, ISI was lower than that in normal weight subgroups (P<0.05). ISI was negatively correlated with body mass index and waist circumference in all groups (P<0.05). ISI was also positively correlated with AIR3-5 in NC group and negatively correlated in the other 3 groups (P<0.05). CONCLUSION: The impact of obesity on insulin secretion is not the same in the subjects with different glucose tolerance. With the aggravation of insulin resistance, the first-phase insulin secretion in the subjects with normal glucose tolerance without family history of diabetes increases for compensation, while that in the normal glucose tolerance subjects who are the first-degree relatives of type 2 diabetic patients, the patients with impaired glucose regulation and the type 2 diabetic patients could not increase for compensation.     

Effects of high glucose on proliferation,migration, adhesion and secretion of rat late endothelial progenitor cells

AIM: To investigate the effects of high glucose on the proliferation, adhesion, migration and secretion potentials of late endothelial progenitor cells (EPCs) from bone marrow. METHODS: Mononuclear cells were collected from rat bone marrow by density gradient centrifugation and cultured with M199 medium. The early EPCs were identified by DiI-ac-LDL and FITC-UEA-1 double staining. The late EPCs were identified by RT-PCR to detect the expression of von Willebrand factor (vWF) and VE-cadherin. Moreover, the cells were identified by FACS to detect the expression of CD133 and vascular endothelial growth factor receptor-2(VEGFR-2). The 3rd generation of EPCs was harvested and incubated with glucose in a series of concentrations (5, 10, 20 or 40 mmol/L). The cell proliferation, adhesion, migration and the secretion of chemokines such as monocyte chemoattractant protein-1(MCP-1) and interleukin-8 (IL-8) were assayed with MTT, adhesion test, modified Boyden chamber assay and ELISA, respectively. RESULTS: Compared with normal glucose (5 mmol/L)treatment, high glucose (10, 20, 40 mmol/L) dose-dependently degraded the proliferation and migration of late EPCs (P<0.05 or P<0.01). At the same time, treatment with glucose at the concentration of 40 mmol/L decreased the adhesion of EPCs (P<0.05) and increased the release of MCP-1 and IL-8 by late EPCs. CONCLUSION: High glucose inhibits proliferation, adhesion and migration of late EPCs, and enhances the secretion of inflammatory factors, indicating that the high glucose correlates with the vascular complications of patients with diabetes.     

白菜冻干粉降糖作用的初步药效学研究

为探讨白菜冻干粉(Chinese Cabbage Freeze-Dried Powder,CCFDP)对高糖高脂饲料饲养小鼠餐后血糖的影响,对血糖筛选合格小鼠分别进行6组处理:正常对照组、高糖高脂饲料饲养造模对照组、造模+同时口服灌胃CCFDP低剂量组、造模+同时口服灌胃CCFDP高剂量组、造模+造模15 d后再同时口服灌胃CCFDP低剂量组、造模+造模15 d后再同时口服灌胃CCFDP高剂量组,45 d后检测小鼠餐后血糖值、血清中总胆固醇(T-CHO)、甘油三酯(TG)、高密脂蛋白(HDL-C)、低密脂蛋白(LDL-C)等指标。结果表明:与模型对照组比较,150 mg/(kg·d)CCFDP能有效降低高糖高脂饲料饲养小鼠的餐后血糖值以及血清TG和LDL-C。CCFDP能显著降低高糖高脂饲料饲养小鼠的餐后血糖,为糖尿病早期防治提供参考。     

Retrospective investigation of perioperative risk factors for immediate postoperative corneal erosions in dogs undergoing phacoemulsification

Objective

To characterize the incidence, contributing risk factors, and healing characteristics of immediate postoperative corneal erosions (IPCE) in dogs undergoing routine phacoemulsification.

Animals Studied

Medical records of 313 canine eyes (159 dogs) undergoing routine phacoemulsification surgery.

Procedures

Medical records of dogs undergoing planned cataract surgery at UW Veterinary Care were retrospectively reviewed. Patient-related variables including age, skull conformation, diabetes status, and cataract stage at the time of surgery were recorded. Intraoperative variables per eye were also recorded including surgical technique, surgeon expertise level, average phacoemulsification power, and phacoemulsification time. Diagnosis of IPCE ≤ 24 h after completion of surgery and time to IPCE healing were recorded where follow-up data were available.

Results

Immediate postoperative corneal erosions were observed in 48/313 (15.3%) operated eyes. The presence of diabetes mellitus or brachycephalic skull conformation, preoperative Schirmer tear test (STT) value, surgical technique and surgeon experience level, phacoemulsification time, and absolute phacoemulsification time were not statistically significant risk factors for IPCE. Average phacoemulsification power was associated with IPCE (RR 1.52, p = .001). Time to IPCE healing was similar in diabetic and non-diabetic dogs (median [IQR] 8 [6–11] days and 8 [6–15] days, respectively). Diabetes mellitus, brachycephaly, and phacoemulsification parameters were not associated with IPCE healing at 7 or 14 days postoperatively.

Conclusions

Higher average phacoemulsification power may be associated with the development of IPCE in canine eyes. The presence of diabetes mellitus or brachycephaly are not risk factors for the development of IPCE, nor are they factors that influence IPCE healing.     

Changes in Glycoprotein Components in Streptozotocin - Nicotinamide Induced Type 2 Diabetes: Influence of Tetrahydrocurcumin from <Emphasis Type="Italic">Curcuma longa</Emphasis>

Curcuma longa (Zingiberaceae) has been used traditionally as antidiabetic, and has been proven scientifically to possess high antioxidant activity and anticancer properties. The active components of Curcuma longa such as curcumin and tetrahydrocurcumin (THC), a major colourless metabolite of curcumin also possesses antidiabetic, antiinflammatory and antioxidant activity. The ethnopharmacological value of this plant, the effect of THC on glycoproteins was carried out in normal and streptozotocin-nicotiniamide induced type 2 hyperglycaemic rats for 45 days. Glucose, plasma insulin and glycoprotein components in plasma and tissues (hexose, hexosamine, fucose and sialic acid) were determined. Oral administration of THC to diabetic rats showed a decrease in the level of blood glucose and plasma glycoproteins. The levels of plasma insulin and tissue sialic acid were increased where as the levels of tissue hexose, hexosamine and fucose were near normal in diabetic rats treated with THC. The present study indicates that the THC possesses a significant beneficial effect on glycoprotein moiety in addition to its antidiabetic effect. The effect of THC is more prominent than curcumin.