Non-fasting Plasma Glucose Levels Research Articles

Salivary glucose levels and oral candidal carriage in type II diabetics

The aim of this study was to detect salivary glucose levels in diabetic and nondiabetic subjects, to study the relationship between salivary glucose levels and salivary candidal carriage, and to determine if salivary glucose levels could be used as a noninvasive tool to monitor glycemic control in diabetics. A total of 150 adults, 100 with type 2 diabetes and 50 without diabetes (control subjects), aged 40-60 years, participated in the study. Diabetic status was determined by estimation of random nonfasting plasma glucose levels and glycosylated hemoglobin levels. Both unstimulated and stimulated saliva were collected and investigated for glucose levels and colony-forming units (CFU) of Candida. Salivary glucose levels were measured using the glucose-oxidase method. Salivary glucose levels were significantly higher in diabetics than nondiabetics. There was a significant positive correlation between salivary and plasma glucose levels. Candidal CFUs were significantly higher in diabetic subjects and showed a significant positive correlation with salivary (unstimulated and stimulated) glucose levels. These results show that salivary glucose concentration is a potentially useful noninvasive tool to monitor glycemic control in diabetic patients. Increased salivary glucose is associated with increased prevalence of oral Candida in these subjects.

Relation of Gamma-Glutamyltransferase and Alcohol Drinking with Incident Diabetes: the HIPOP-OHP Study

Gamma-glutamyltransferase (GGT) is known to correlate well with alcohol consumption; however, the relation between GGT and diabetes and that between alcohol consumption and diabetes mellitus (DM) is inconsistent. Thus, several questions, such as whether light to moderate drinkers can be considered as low risk for diabetes incidence irrespective of their GGT level, is unresolved. In this study, we investigated the relation of GGT or alcohol drinking with DM incidence considering the body mass index (BMI) in healthy Japanese workers. We followed 3095 men who did not have DM at baseline for 4 years. Incident diabetes was defined as a fasting (non-fasting) plasma glucose level of >or=7.0 (11.1) mmol/L, or treatment of diabetes. Multiple adjusted hazard ratios (HR) were calculated using Cox proportional models. Participants with higher GGT (GGT >or=27 IU/L) showed an increased risk of diabetes incidence even when their BMI level was low. Although a U-shaped relation between alcohol drinking and incident diabetes was observed, the risk to light to moderate drinkers (alcohol <23 g/day) was not low if they were either overweight (BMI >or=25 kg/m(2)) or had higher GGT (HR=2.60, p=0.08) or both overweight and higher GGT (HR=3.16, p=0.07) compared with never drinkers without higher GGT and overweight. Higher GGT was associated with a higher incidence of DM irrespective of drinking status or obesity. Although a U-shaped relation between alcohol drinking and incident diabetes was observed, the risk to light to moderate drinkers was not low if they were either overweight or had higher GGT.

Glucose as a prognostic factor in non-diabetic women with locally advanced cervical cancer (IIB–IVA)

Objective The aim of this study was to evaluate the association between pretreatment random plasma glucose levels and cancer prognosis in non-diabetic women with locally advanced cervical cancer treated with CCRT (concurrent chemoradiation) or RT (radiation therapy) only. Methods We investigated the non-fasting plasma glucose levels checked during the initial work up before treatment in 134 non-diabetic patients with locally advanced cervical cancer. Based on the survival time and the progression-free interval (PFI) recorded in the electronic medical records Cox proportional hazard regression models were used to estimate the hazard ratio (HR) for overall survival and PFI according to the various level of glucose and a cut-off level (< 102 mg/dL and ≥ 102 mg/dL), adjusting for clinical covariates. Results A shorter overall survival and PFI was observed in the group with higher glucose levels (HR, 1.03; p = 0.002, HR, 1.02; p = 0.001, respectively) and more than 102 mg/dL, by univariate analyses (HR, 3.21; p = 0.012, HR, 2.20; p = 0.006, respectively). Multivariate analysis, adjusting for clinical FIGO stage, performance status, treatment type (CCRT vs. RT) and chemotherapeutic regimen types showed that patients with higher glucose levels or more than ≥ 102 mg/dL had shorter overall survival times (HR, 1.02; p = 0.015, HR, 2.54; p = 0.049, respectively) and PFI (HR, 1.02; p = 0.003, HR, 1.88; p = 0.031, respectively). Conclusion This investigation provides evidence supporting the prognostic value of glucose levels in non-diabetic women with locally advanced cervical cancer treated with radiation therapy and/or concurrent chemotherapy; high glucose levels were associated with a greater risk for recurrence and mortality in these patients.

P21: Unique histopathological characteristics of diabetic ocular lesions in both sexes of the Spontaneously Diabetic Torii (SDT) rat

The Spontaneously Diabetic Torii (SDT) rat is a novel rat model recently established for type 2 diabetes mellitus. The rats develop hyperglycemia (non-fasting plasma glucose level in males at 25 weeks: about 700 mg/dL) but can survive for long period of time without insulin therapy. The onset of diabetes is as early as 15 weeks of age in males and 40 weeks in females. The cumulative incidence of diabetes reaches 100% by 40 weeks of age in males, however, only 33% of female SDT rats develop diabetes by 65 weeks of age. To elucidate the histopathologic characteristics of the diabetic ocular lesions and the gender difference of the lesions, eyes of various ages from 23 SDT rats (twelve males of 39–70 weeks, mean, 63 weeks; eleven females 60–82 weeks, mean, 67 weeks) kept without any treatment were examined. Histopathologically, severe diabetic ocular lesions including cataracts (total incidence, 23/23:100%), rapture of the lens (57%), posterior vitreous detachment (83%), proliferative retinopathy (57%), tractional retinal detachment (74%) and iris neovascularization (83%) were observed in both sexes. In one case of 64-week-old male, a massive anterior chamber hemorrhage was observed. The onset of diabetes is about 6 months later in females, however, the diabetic ocular lesions were similar in females and males at ages over 60 weeks. Female SDT rats suffered from impaired glucose tolerance (IGT) as early as 25 weeks of age and over a long period of time of IGT in females may relate to the progressive development of the lesions. In conclusion, SDT rats of both sexes can develop similar ocular complications, which closely mimic morphologically those reported in diabetic patients. The SDT rats represent the first animal model for diabetic ocular complications.

Lower Frequency of Daily Teeth Brushing Is Related to High Prevalence of Cardiovascular Risk Factors

This study sought to investigate relationships between frequency of daily teeth brushing and prevalences of diabetes mellitus, hypertension and dyslipidemia. Subjects were 54,551 residents of Chiba City, Japan (20,155 men and 34,396 women) who underwent routine health examinations in 2004. Diabetes mellitus was defined as a fasting plasma glucose level > or =126 mg/dl or a non-fasting plasma glucose level > or =200 mg/dl and/or receiving treatment for diabetes. Hypertension was defined as systolic blood pressure (SBP) > or =140 mmHg, diastolic blood pressure (DBP) > or =90 mmHg and/or receiving treatment for hypertension. Dyslipidemia was defined according to the two criteria: high triglyceride and/or low high density lipoprotein cholesterol (TG > or = 150 mg and/or HDL-C < 40 mg/dl), and high total cholesterol (TC > or = 220 mg/dl). According to Pearson's chi-square tests and logistic regression analysis adjusted for age, BMI, smoking habit, alcohol consumption and daily walking time, lower frequency of teeth brushing is related to higher prevalences of diabetes mellitus, hypertension and high TG and/or low HDL-C, in both men and women. Total cholesterol status, however, showed no significant relationship. Maintaining good oral hygiene by regular teeth brushing may prevent type 2 diabetes, hypertension and dyslipidemia.

Polymorphisms at newly identified lipid-associated loci are associated with blood lipids and cardiovascular disease in an Asian Malay population

We conducted a cross-sectional study of Malay participants aged 40-80 years (n = 2,932) to examine the associations between polymorphisms at newly identified, lipid-associated loci with blood lipid levels and prevalent cardiovascular disease (CVD) in a Malay population in Asia. A polymorphism adjacent to the TRIB1 locus (rs17321515) was associated with elevated total cholesterol and LDL-cholesterol (LDL-C) after adjustment for age and sex (both P values <0.007) and with increased risk of coronary heart disease and CVD [odds ratio (OR) 1.23, 95% confidence interval (95% CI) 1.03-1.46; and OR 1.2, 95% CI 1.02-1.42, respectively] under an additive model of inheritance. In addition, using recessive models of inheritance, polymorphisms on chromosome 19 adjacent to the CILP2 and PBX4 loci (rs16996148) and on chromosome 1 at the GALNT2 locus (rs4846914) were associated with elevated HDL-C (P = 0.005) and lower LDL-C (P = 0.048), respectively. Although novel, the former is consistent with the association between this polymorphism and lower blood triglycerides observed in the initial studies conducted in populations of European ancestry. Neither showed statistically significant association with CVD. These observations should form the basis of further investigation to identify the causative polymorphisms at this locus, and also to understand the mechanistic roles that this protein may play in lipoprotein metabolism in Asians and other populations.

Glucose as a prognostic factor in ovarian carcinoma

Research suggests that glucose levels in cancer patients may be an important prognostic indicator. In ovarian tumors, increased expression of glucose transporter 1 (GLUT1), a transmembrane protein responsible for glucose uptake, is related to shorter survival time in ovarian cancer patients. This study tested the hypothesis that higher presurgical glucose levels predict shorter disease-specific survival time and time to recurrence in ovarian cancer patients. Nonfasting plasma glucose levels were determined for 74 patients with ovarian cancer at the time of their presurgical consultation and for 125 ovarian cancer patients in an independent validation set. Survival time and time to recurrence (disease-free interval [DFI]) were ascertained from medical records. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) for survival time and DFI in relation to glucose level, adjusting for body mass index (BMI), stage, grade, and cytoreduction as appropriate. Higher glucose levels were associated with shorter survival times in univariate analyses (HR, 1.88; P = .05). Multivariate analysis adjusting for stage showed that higher glucose levels were associated with shorter survival times (HR, 2.01; P = .04) and DFI (HR, 2.32; P = .05). In the validation set, higher glucose levels were associated with shorter survival times (HR, 2.01; P = .02) and DFI (HR, 2.48; P = .001) in univariate analysis, although glucose was not independent of the effect of cytoreduction when predicting survival time in this latter set. These findings contribute to mounting evidence that glucose levels have prognostic value in ovarian carcinoma.

Gender Differences in Endothelial Function in Aortas From Type 2 Diabetic Model Mice

Type 2 diabetes mellitus is associated with high mortality and morbidity, mainly due to coronary artery disease and atherosclerosis, although female gender is a protective factor in the development of, for example, atherosclerosis and hypertension. Our main aim was to investigate gender differences in endothelial function in aortas from type 2 diabetic model mice. The nonfasting plasma glucose level was significantly elevated in diabetic mice (both males and females). The plasma insulin level was not different between controls and diabetics (either gender). The plasma adiponectin level was decreased by diabetes, and was lower in males. In control aortas (from males or females), the clonidine-induced relaxation was abolished by Akt-inhibitor treatment. In diabetic males (versus both control males and diabetic females): a) the clonidine- and insulin-induced endothelium-dependent aortic relaxations were impaired, but the acetylcholine (ACh)–induced and sodium nitroprusside (SNP)–induced aortic relaxations were not, b) the norepinephrine (NE)–induced aortic contractile response was enhanced, c) systemic blood pressure was elevated, and d) the clonidine-stimulated Ser-473 phosphorylation of Akt in the aorta was decreased. These results suggest that endothelial functions dependent on the Akt pathway are abrogated by type 2 diabetes only in male mice.

Sub-chronic administration of the 11β-HSD1 inhibitor, carbenoxolone, improves glucose tolerance and insulin sensitivity in mice with diet-induced obesity

We have examined the metabolic effects of daily administration of carbenoxolone (CBX), a naturally occurring 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) inhibitor, in mice with high fat diet-induced insulin resistance and obesity. Eight-week-old male Swiss TO mice placed on a synthetic high fat diet received daily intraperitoneal injections of either saline vehicle or CBX over a 16-day period. Daily administration of CBX had no effect on food intake, but significantly lowered body weight (1.1- to 1.2-fold) compared to saline-treated controls. Non-fasting plasma glucose levels were significantly decreased (1.6-fold) by CBX treatment on day 4 and remained lower throughout the treatment period. Circulating plasma corticosterone levels were not significantly altered by CBX treatment. Plasma glucose concentrations of CBX-treated mice were significantly reduced (1.4-fold) following an intraperitoneal glucose load compared with saline controls. Similarly, after 16-day treatment with CBX, exogenous insulin evoked a significantly greater reduction in glucose concentrations (1.4- to 1.8-fold). 11beta-HSD1 gene expression was significantly down-regulated in liver, whereas glucocorticoid receptor gene expression was increased in both liver and adipose tissue following CBX treatment. The reduced body weight and improved metabolic control in mice with high fat diet-induced obesity upon daily CBX administration highlights the potential value of selective 11beta-HSD1 inhibition as a new route for the treatment of type 2 diabetes and obesity.

Metabolic effects of sub-chronic ablation of the incretin receptors by daily administration of (Pro3)GIP and exendin(9–39)amide in obese diabetic (ob/ob) mice

Effects of chemical ablation of the GIP and GLP-1 receptors on metabolic aspects of obesity-diabetes were investigated using the stable receptor antagonists (Pro3)GIP and exendin(9-39)amide. Ob/ob mice received a daily i.p. injection of saline vehicle, (Pro3)GIP, exendin(9-39)amide or a combination of both peptides over a 14-day period. Non-fasting plasma glucose levels were significantly (p<0.05) lower in (Pro3)GIP-treated mice compared to control mice after just 9 days of treatment. (Pro3)GIP-treated mice also displayed significantly lower plasma glucose concentrations in response to feeding and intraperitoneal administration of either glucose or insulin (p<0.05 to p<0.001). The (Pro3)GIP-treated group also exhibited significantly (p<0.05) reduced pancreatic insulin content. Acute administration of exendin(9-39)amide immediately prior to re-feeding completely annulled the beneficial effects of sub-chronic (Pro3)GIP treatment, but non-fasting concentrations of active GLP-1 were unchanged. Combined sub-chronic administration of (Pro3GIP) with exendin(9-39)amide revealed no beneficial effects. Similarly, daily administration of exendin(9-39)amide alone had no significant effects on any of the metabolic parameters measured. These studies highlight an important role for GIP in obesity-related forms of diabetes, suggesting the possible involvement of GLP-1 in the beneficial actions of GIP receptor antagonism.

Capsaicin‐sensitive sensory fibers in the islets of Langerhans contribute to defective insulin secretion in Zucker diabetic rat, an animal model for some aspects of human type 2 diabetes

The system that regulates insulin secretion from beta-cells in the islet of Langerhans has a capsaicin-sensitive inhibitory component. As calcitonin gene-related peptide (CGRP)-expressing primary sensory fibers innervate the islets, and a major proportion of the CGRP-containing primary sensory neurons is sensitive to capsaicin, the islet-innervating sensory fibers may represent the capsaicin-sensitive inhibitory component. Here, we examined the expression of the capsaicin receptor, vanilloid type 1 transient receptor potential receptor (TRPV1) in CGRP-expressing fibers in the pancreatic islets, and the effect of selective elimination of capsaicin-sensitive primary afferents on the decline of glucose homeostasis and insulin secretion in Zucker diabetic fatty (ZDF) rats, which are used to study various aspects of human type 2 diabetes mellitus. We found that CGRP-expressing fibers in the pancreatic islets also express TRPV1. Furthermore, we also found that systemic capsaicin application before the development of hyperglycemia prevents the increase of fasting, non-fasting, and mean 24-h plasma glucose levels, and the deterioration of glucose tolerance assessed on the fifth week following the injection. These effects were accompanied by enhanced insulin secretion and a virtually complete loss of CGRP- and TRPV1-coexpressing islet-innervating fibers. These data indicate that CGRP-containing fibers in the islets are capsaicin sensitive, and that elimination of these fibers contributes to the prevention of the deterioration of glucose homeostasis through increased insulin secretion in ZDF rats. Based on these data we propose that the activity of islet-innervating capsaicin-sensitive fibers may have a role in the development of reduced insulin secretion in human type 2 diabetes mellitus.

Metabolic syndrome and urinary cGMP excretion in general population

To examine the relationship between metabolic syndrome and endothelial dysfunction, we investigated cross-sectionally the correlation between metabolic risk factors and urinary excretion of cyclic guanosine 3′,5′-monophosphate (cGMP), a second messenger of nitric oxide (NO), in 1541 Japanese men and women aged 40–79 years. The 24-h urinary excretion of cGMP was measured using a 125I-labeled cGMP radioimmunoassay and was adjusted for urinary creatinine excretion (nmol/mmol creatinine). The components of metabolic syndrome were defined based on the following criteria: body mass index (BMI) ≥ 25.0 kg/m 2, fasting plasma glucose ≥ 6.11 mmol/l or non-fasting plasma glucose level ≥ 11.1 mmol/l, systolic blood pressure ≥ 130 mm Hg or diastolic blood pressure ≥ 85 mm Hg, high-density lipoprotein (HDL)-cholesterol < 1.03 mmol/l for men and <1.29 mmol/l for women, and triglyceride ≥ 1.69 mmol/l. The number of components of metabolic syndrome correlated inversely with urinary cGMP excretion; means of cGMP excretion for the whole group adjusted for age, sex, and cardiovascular risk factors were 53.6, 48.6, 47.9, 44.4 and 42.3 nmol/mmol for 0, 1, 2, 3, and 4–5 components of metabolic syndrome, respectively ( p = 0.002). Our data suggest that a reduction of NO bioactivity concur with clustered features of the metabolic syndrome.

Prevalence of diabetes mellitus in chronic schizophrenic inpatients in relation to long-term antipsychotic treatment

Background Many reports indicate that the incidence and prevalence of diabetes mellitus is increased in schizophrenic patients and related to antipsychotic treatment. In an exploratory cross-sectional study we assessed the prevalence of type 2 diabetes mellitus in 266 chronic schizophrenic and schizoaffective inpatients and investigated whether the duration of antipsychotic treatment was related to the development of diabetes mellitus. Method We measured the non-fasting plasma glucose level in 266 inpatients with DSM IV diagnosis of schizophrenia or schizoaffective disorder in 5 different long-stay wards in the Netherlands. Measured variables were: age, sex, ethnicity, BMI, current antipsychotic treatment, duration of illness and duration of antipsychotic treatment. Results The overall prevalence of type 2 diabetes mellitus was 9%, which is significantly higher than the prevalence of 4.9% in the general population (OR 1.89, CI 1.14–3.13; p < 0.014). The prevalence was increased in two age cohorts: 30–39 years (3.8% vs. 0.3%, OR = 13.29, CI = 2.17–81.36, p = < 0.005) and 40–49 years (9.3% vs. 1.5%, OR = 6.74, CI = 2.77–16.38, p = 0.000). No new cases of diabetes mellitus were detected during the course of the study. The increased prevalence was found to be related to overweight and obesity. The time of exposure to antipsychotic treatment was not significantly correlated with the prevalence of diabetes mellitus when adjusted for age ( F = 0.804, df = 1, p = 0.371, respectively, F = 0.194, df = 1, p = 0.660). Both typical and atypical antipsychotics contributed equally to the prevalence of diabetes mellitus. Conclusion No significant relation between long-term antipsychotic treatment and prevalence of diabetes mellitus was found. The high prevalence of diabetes mellitus in schizophrenic patients warrants screening of these patients already at young age for glucose disturbance.

Chemical Ablation of Gastric Inhibitory Polypeptide Receptor Action by Daily (Pro3)GIP Administration Improves Glucose Tolerance and Ameliorates Insulin Resistance and Abnormalities of Islet Structure in Obesity-Related Diabetes

Glucose-dependent insulinotropic polypeptide (gastric inhibitory polypeptide [GIP]) is an important incretin hormone secreted by endocrine K-cells in response to nutrient ingestion. In this study, we investigated the effects of chemical ablation of GIP receptor (GIP-R) action on aspects of obesity-related diabetes using a stable and specific GIP-R antagonist, (Pro3)GIP. Young adult ob/ob mice received once-daily intraperitoneal injections of saline vehicle or (Pro3)GIP over an 11-day period. Nonfasting plasma glucose levels and the overall glycemic excursion (area under the curve) to a glucose load were significantly reduced (1.6-fold; P < 0.05) in (Pro3)GIP-treated mice compared with controls. GIP-R ablation also significantly lowered overall plasma glucose (1.4-fold; P < 0.05) and insulin (1.5-fold; P < 0.05) responses to feeding. These changes were associated with significantly enhanced (1.6-fold; P < 0.05) insulin sensitivity in the (Pro3)GIP-treated group. Daily injection of (Pro3)GIP reduced pancreatic insulin content (1.3-fold; P < 0.05) and partially corrected the obesity-related islet hypertrophy and beta-cell hyperplasia of ob/ob mice. These comprehensive beneficial effects of (Pro3)GIP were reversed 9 days after cessation of treatment and were independent of food intake and body weight, which were unchanged. These studies highlight a role for GIP in obesity-related glucose intolerance and emphasize the potential of specific GIP-R antagonists as a new class of drugs for the alleviation of insulin resistance and treatment of type 2 diabetes.

Amelioration of the beta-cell dysfunction in diabetic APA hamsters by antioxidants and AGE inhibitor treatments.

In our recent report, probucol treatment ameliorated glucose intolerance and increased the insulin-positive area in the pancreas of streptozotocin (SZ)-induced diabetic APA hamsters. The data suggested that the beneficial effects of probucol treatment on beta-cell function might result from its additive effect as an antioxidant. Here, we examined the antioxidant effects on the beta-cell function in SZ-induced diabetic APA hamsters treated with three different agents, N-acetyl-L-cysteine (NAC), aminoguanidine (AG) and pyridoxamine (PM). The control (CB group) and diabetic (SZ group) hamsters were treated with NAC, AG or PM for four weeks from several days after SZ injection. Non-fasting plasma glucose and glycoalbumin levels were significantly reduced in SZ animals by NAC or PM treatment. Glucose tolerance test revealed that fasting plasma glucose levels of SZNAC and SZPM animals were low, similar to the corresponding control animals. Thirty minutes after glucose injection, amelioration in the plasma glucose levels of SZNAC and SZPM animals was observed. Immunohistochemistry revealed that the pancreata of SZNAC, SZAG and SZPM animals showed significantly higher percentages of insulin-positive area than those of non-treated SZ animals. The plasma 8OHdG and malondialdehyde plus 4-hydroxy-2-nonenal (4HNE) levels were significantly decreased especially in SZNAC and SZPM animals. 4HNE-positive cells stained by anti-4HNE antibody were reduced in the islets of each agent-treated animal. SZNAC and SZPM animals showed significantly increased beta-cell proliferation determined by insulin and BrdU double staining. All SZ groups treated with NAC, AG or PM had the high expression levels of Reg and INGAP, which are known to be expressed in regenerating islets. These data suggest that NAC and PM treatment of SZ-injected diabetic hamsters reduces oxidative stress and restores beta-cell function, but that AG treatment has little beneficial effect on the diabetic conditions of SZ-injected hamsters.

Simultaneous Pancreaticoduodenal-Kidney Transplantation in Rats

Aims: To establish a stable and simple simultaneous pancreaticoduodenal-kidney transplantation model in rats. Methods: Pancreaticoduodenal-kidney (left) and 1 cm of the inferior vena cava (IVC) with 0.5 cm left and right iliac communis vein were harvested from donors. We performed ‘cuff’ anastomoses between (1) portal vein and right iliac communis vein and (2) left kidney vein and left iliac communis vein, converging donor portal vein and left kidney vein into IVC together. Next, we performed an anastomosis of donor arterial segment and recipient abdominal aorta and a ‘cuff’ anastomosis between donor IVC and recipient left kidney vein. Results: Of 40 transplanted rats in which diabetes was induced, 33 survived over 7 days, and 31 rats have survived over 4 months. 30 rats’ nonfasting plasma glucose levels were euglycemic. Conclusions: We performed three ‘cuff’ anastomoses to simplify the surgical procedure and to shorten the ischemic period of the graft. The recipient vein system has an integrated membrane to avoid thrombi in venous anastomosis sites, enhancing the transplantation success rate.

Combined pancreaticoduodenal-kidney transplantation in rats.

The objective of this work was to establish a stable and simple simultaneous pancreaticoduodenal-kidney transplantation model in rats. The methods involved harvesting a pancreaticoduodenal-kidney (left) (PDK) and 1-cm inferior vena cava (IVC) with a 0.5-cm left and right iliac communis vein from donors and to "cuff" anastomose between portal vein and right iliac communis vein, left kidney vein, and left iliac communis vein, converging donor portal vein and left kidney vein into IVC together. Next, we performed an anastomosis of the donor arterial segment and recipient abdominal aorta and a "cuff" anastomosis between donor IVC and recipient left kidney vein. Of 67 transplanted rats in which diabetes was induced, 57 survived >7 days, 55 survived 1 month, 54 rats have survived >4 months. In 51 rats, nonfasting plasma glucose levels were euglycemic. We performed three "cuff" anastomoses to simplify the surgical procedure and to shorten the ischemia time of the graft; the recipient vein system has an integrated endovenous membrane to avoid venous thrombi in venous anastomosis sites.

Extrapancreatic action of truncated glucagon-like peptide-I in otsuka long-evans tokushima fatty rats, an animal model for non—insulin-dependent diabetes mellitus

To clarify the mechanism(s) of the antidiabetic effects of truncated glucagon-like peptide-1 (GLP-1) in diabetics, we examined its insulinotropic and extrapancreatic effects in a newly established strain of spontaneously non—insulin-dependent diabetic (NIDDM) rats, Otsuka Long-Evans Tokushima Fatty (OLETF) rats, that received a continuous infusion of truncated GLP-1 620 pmol/d/kg (G group, n = 12) or of vehicle (V group, n = 12) for 4 weeks by Alzet pump. Nonfasting plasma glucose levels were significantly lower ( P < .05) in the G group than in the V group (7.0 ± 0.67 v 9.1 ± 1.7 mmol/L), and fasting plasma immunoreactive insulin (IRI) levels were lower in the former than in the latter (0.63 ± 0.31 v 0.78 ± 0.25 nmol/L). At day 15 of infusion, the G group showed an attenuated plasma glucose response to an oral glucose load, but had plasma IRI levels comparable to those in the V group. A long-term infusion of truncated GLP-1 increased the glucose infusion rate (GIR) significantly ( P < .05) during a euglycemic-hyperinsulinemic clamp test (59.0 ± 14.8 μmol/kg/min for group G v 38.9 ± 12.2 for group V), but hepatic glucose output (HGO) did not differ significantly for either group. Uptake of 2-deoxy- d-glucose (2DG) by peripheral muscles in the G group was as much as 2.4-fold higher than in the V group (5.52 ± 2.04 v 2.29 ± 0.97 μmol/100 g muscle weight/min). We conclude from these data that truncated GLP-1, in addition to its well-known incretin effect, is capable of augmenting insulin action in peripheral tissues of diabetics, which can contribute, in part, to improve glucose intolerance in OLETF rats.

Long‐term culture, low‐temperature culture, and hyperoxic culture do not prolong fish‐to‐mouse islet xenograft survival

Abstract: Macroscopic, anatomically discrete islets called Brockmann bodies (BB) were harvested from tilapia with microscissors and then cultured under various conditions known to prolong islet allograft survival. BBs were cultured in 95% air/5% CO2 at 37°C either overnight (groups 1 and 2) or for 1 week (group 3); in 95% O2/5% CO2 at 37°C for 1 week (group 4), or in 95% air/5% CO2 at 24°C for 1 week (groups 5 and 6). Viability and function of cultured islets was confirmed by fluorescein diacetate/ethidium bromide staining and by transplantation under the left renal capsules of streptozotocin‐diabetic balb/c mice. Recipient mice in groups 2 and 6 received CsA (50 mg/kg/d p.o.) × 4 days. All recipient mice became normoglycemic posttransplant. Mean graft survival times (± S.D.) for groups 1, 2, 3, 4, 5, and 6 were 7.6 (± 1.1), 6.2 (± 1.5), 6.4 (± 0.79), 8.2 (± 2.3), 7.0 (± 0.71), and 6.2 (± 0.45) days, respectively. Rejection (i.e., nonfasting plasma glucose levels &gt; 200 mg/dl) was confirmed histologically in all instances; rejection was characterized by infiltrates composed of mononuclear cells, plasma cells, and eosinophils. In our study, neither short‐term CsA nor any of the culture protocols significantly prolonged discordant fish‐to‐mouse islet xenograft survival.

A study of effect of CS-045, a new antidiabetic drug, on hypertension in spontaneously hypertensive rat.

Several lines of evidence have suggested that insulin resistance may play an important role in the pathogenesis of hypertension. CS-045 is a new hypoglycemic drug by which improves insulin sensitivity in peripheral tissues. We assessed the effect of CS-045 on hypertension in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) as a control. At 20 weeks of age, the treatment with CS-045 was started by being mixed with chow pellets in the proportion of 0.2% (w/w) and continued for 6 weeks. Nonfasting plasma glucose levels were not changed in either strain of rats treated with CS-045, but plasma insulin levels decreased in SHR 4 and 5 weeks after the start of CS-045 therapy. Blood pressure increased with age in SHR without treatment, but CS-045 decreased blood pressure only 4 and 6 weeks after the treatment. These findings suggest that insulin resistance is not strongly associated with the pathogenesis of hypertension in SHR.