T Utsugi, T Kanda, Y Tajima, S Tomono, T Suzuki, K Murata, K Dan, Y Seto, S Kawazu
{"title":"A new animal model of non-insulin-dependent diabetes mellitus induced by the NDK25 variant of encephalomyocarditis virus.","authors":"T Utsugi, T Kanda, Y Tajima, S Tomono, T Suzuki, K Murata, K Dan, Y Seto, S Kawazu","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Intraperitoneal inoculation with NDK25, a variant of Encephalomyocarditis (EMC) virus which has been newly cloned from the M variant of EMC virus (EMC-M), caused DBA/2 mice to develop noninsulin-dependent diabetes mellitus. The NDK25-infected mice demonstrated abnormal glucose tolerance from 1 to 3 weeks after inoculation. The infection resulted in mild insulitis and the destruction of pancreatic beta cells at 1 week after inoculation and led to a significant reduction in the insulin content of the pancreas, but there was no ketonuria. The insulin content of the pancreas was recovered considerably from 15 +/- 3 at 1 week to 95 +/- 16 micrograms/g pancreas at 12 weeks, although the latter value was still significantly lower than that of the control mice (P < 0.05). Under microscopy, mild and partial infiltration of mononuclear cells was observed in about half the pancreatic islets only 1 week after inoculation, and then disappeared. Thus, we believe we have established a new model of noninsulin-dependent diabetes mellitus using the NDK25 variant of EMC virus.</p>","PeriodicalId":77108,"journal":{"name":"Diabetes research (Edinburgh, Scotland)","volume":"20 4","pages":"109-19"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12517512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Brain catecholamine concentrations in hyperosmolar diabetic and diabetic rats.","authors":"Y Tasaka, H Matsumoto, Y Inoue, Y Hirata","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The concentration of brain catecholamines were measured and compared in the experimentally made hyperosmolar diabetic, diabetic and normal control rats in order to clarify the metabolic changes of the brain in these states. Diabetes was induced with streptozotocin and hyperosmolarity was achieved through deprivation of water for 50 hours prior to experimentation. Dopamine, norepinephrine and epinephrine concentrations were measured in the left cerebral cortex, hypothalamic-thalamic area, cerebellum and medulla oblongata. Dopamine and norepinephrine concentrations were significantly elevated in the cerebral cortex, hypothalamic-thalamic area and cerebellum of the dehydrated hyperosmolar-diabetic rats relative to those of normal controls (p < 0.01-0.05). In diabetes with high blood sugar level, the norepinephrine concentration was significantly elevated in the cerebral cortex, cerebellum and medulla oblongata, and these changes generally paralleled the increase in fasting blood glucose. It was concluded that hyperosmolarity due to dehydration contributed these changes. The findings of this study further suggest that changes in brain catecholamines may be involved in the nervous system disturbances that occur in the dehydrated hyperosmolar-diabetes and severe diabetes.</p>","PeriodicalId":77108,"journal":{"name":"Diabetes research (Edinburgh, Scotland)","volume":"19 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12637359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N H Schut, E C van Arkel, M R Hardeman, H J Bilo, R P Michels, J Vreeken
{"title":"Blood and plasma viscosity in diabetes: possible contribution to late organ complications?","authors":"N H Schut, E C van Arkel, M R Hardeman, H J Bilo, R P Michels, J Vreeken","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>It has been postulated that an increased whole blood and plasma viscosity contribute to diabetic organ complications. Blood viscosity was measured in 30 controls and four groups of insulin-dependent diabetic patients at three shear rates: 70 sec-1, 0.5 sec-1 and 0.05 sec-1. Results were compared before and after correction for a haematocrit of 0.45. Twenty-five patients without organ complications, 21 with microalbuminuria, 13 with overt nephropathy and 12 patients with leg ulcerations were studied. Blood and plasma viscosity were normal in the patients without organ complications and with microalbuminuria. Plasma viscosity was significantly elevated in the diabetic patient with nephropathy and leg ulceration. After correction for haematocrit blood viscosity was also higher in these two groups, although this was only significant in the group with leg ulceration. In conclusion blood and plasma viscosity were only elevated in the patients with major organ complications and not in the patients without or with early complications. Therefore it is unlikely that an elevation of blood or plasma viscosity contributes early in the pathogenesis of diabetic organ damage.</p>","PeriodicalId":77108,"journal":{"name":"Diabetes research (Edinburgh, Scotland)","volume":"19 1","pages":"31-5"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12637361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J R Lakey, A B Thomson, M Keelan, G L Lopaschuk, M T Clandinin, C I Cheeseman, R V Rajotte
{"title":"Dietary lipid content influences the clinical and intestinal adaptive responses to islet transplantation in diabetic rats.","authors":"J R Lakey, A B Thomson, M Keelan, G L Lopaschuk, M T Clandinin, C I Cheeseman, R V Rajotte","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Nutrient absorption is increased in rats with streptozotocin-induced diabetes mellitus (DM). This intestinal adaptive response is modified by isocaloric manipulations of the dietary content of fatty acids, and separate studies have shown a normalization of the enhanced uptake of glucose and lipids when DM rats are treated with transplantation of 3000 syngeneic pancreatic islets of Langerhans. These studies were undertaken to test the hypothesis that modification of the type of fatty acids in the triglycerides in isocaloric semisynthetic diets (S, saturated fatty acids from beeftallow; or F, polyunsaturated fatty acids from fish oil) fed to DM recipients influences the ability of syngeneic transplanted islets to normalize the clinical indices of glycemic control and the intestinal adaptive response. A suboptimal number of islets was transplanted (1200) under the renal capsule, so that the clinical parameters of diabetic control would be modestly abnormal and so that any possible beneficial influence of this dietary manipulation might better be able to demonstrate a further improvement of clinical endpoints. Adult Male Wistar-Furth rats were rendered diabetic, transplanted with 1200 syngeneic islets, and were then fed for 6 weeks a chow or a isocaloric semisynthetic diet enriched with either S or F. Islet transplantation reduced the diabetes-associated abnormalities in food consumption, body weight gain, intestinal weight, urine glucose concentrations, urine volume, oral glucose tolerance, hemoglobin A1c and blood urea nitrogen concentration; these changes were all similar in transplanted animals fed S, F, or chow. Plasma concentrations of cholesterol and triglycerides were significantly elevated in transplanted rats fed S as compared to those fed F or chow. Transplanted DM rats had reduced in vitro intestinal uptake of stearic, oleic, linoleic and linolenic fatty acids, and cholesterol as compared with untreated DM rats, but the uptake of lipids was similar in transplanted DM rats fed S, F, or chow diets. Feeding rats S prevented the decline in the value of the jejunal maximal transport rate (Vmax) and apparent Michaelis affinity constant (Km) observed in transplanted DM rats fed F, but the lack of difference in glycemic control in transplanted DM rats fed F was likely due to their higher ileal Vmax for glucose uptake. Thus, intestinal adaptive function and clinical glycemic control are influenced by the type of fatty acids fed to syngeneic islet-transplanted DM rats.</p>","PeriodicalId":77108,"journal":{"name":"Diabetes research (Edinburgh, Scotland)","volume":"19 4","pages":"149-64"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12516873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of dietary protein and fat source on the development of insulin-dependent diabetes in the BB rat.","authors":"J Hoorfar, K Buschard, C H Brogren","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Epidemiological studies show a remarkable geographical difference in the prevalence of IDDM, suggesting a role for environmental factors such as diet, infection, or stress in the etiology of the disease. Dietary modification has already been shown to be effective in the prevention of autoimmune diabetes in the BB rat and NOD mouse. We studied the effect of protein and fat source in the prophylaxis of diabetes in the BB rat. Natural ingredient rat chow was consistently associated with a high expression of the disease, whereas a casein-based, defined diet significantly inhibited the development of diabetes. Substitution of casein with raw red lentils resulted in a markedly higher incidence. This is the first highly diabetogenic defined diet in the BB rat. Neither fish oil nor soy oil enhanced diabetes expression in the BB rat. Increased amounts of soy oil also did not influence the disease process. These results suggest a central role for dietary protein source in the pathogenesis of BB rat diabetes. We speculate that plant proteins containing anti-nutrients such as chemicals, lectins, enzyme inhibitors, and nonphysiologic amino acids may initiate or hasten the pathogenesis process via beta cell stress or immune response activation.</p>","PeriodicalId":77108,"journal":{"name":"Diabetes research (Edinburgh, Scotland)","volume":"20 1","pages":"33-41"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12518448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Streptozotocin-induced diabetes and the effects of endurance exercise training.","authors":"C E Riggs, G Collins, M Taylor","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The purpose of this investigation was to determine if endurance exercise training would alter the degenerative effects of streptozotocin diabetes on cardiac function and alter the responses of streptozotocin diabetic rats to induced myocardial ischemia. Diabetic rats experienced a significant (p < 0.05) reduction in cardiac function as evidenced by left ventricular peak systolic pressure (LVPSP), maximal time rate of change of pressure (+dP/dTmax), rate pressure product (RPP), and heart rate (HR). Exercise training apparently reduced the effect of diabetes since the function of non-ischemic hearts from trained diabetic rats was not different from that of non-diabetic rats. It also was not different from the sedentary diabetic rat hearts. Training did not alter the response of the hearts of either group of diabetic rats to induced myocardial ischemia.</p>","PeriodicalId":77108,"journal":{"name":"Diabetes research (Edinburgh, Scotland)","volume":"19 4","pages":"177-85"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12516875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Monoclonal antibodies raised against semi-purified preparations of human islets define subpopulations of pancreatic cells.","authors":"S M Swift, J Rowe, A P Larkins, R F James","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Monoclonal antibodies were produced from fusions between splenocytes from BALB/c mice immunised with purified human islets and the mouse myeloma cell line NS-0/Uncl. Supernatants from uncloned hybrids were screened by immunohistology on frozen sections of human pancreas. The range of specificities appeared to reflect the relative purity of the human islet preparations used. Eight monoclonal antibodies were investigated further, four of these bound to islet cells, two to acinar cells, one to ductal cells and one to occasional cells. The antigens recognised by these antibodies were characterised by immunohistology using a number of different tissues, as well as haemagglutination, immunoblotting and radioimmunoassay for insulin. Seven of the eight antibodies studied were IgM. One acinar cell antibody (IgG2a) precipitated proteins of 200Kd and 11OKd molecular weight. None of the antibodies bound directly to insulin. Seven of the antibodies appear to have defined previously unreported epitopes in the pancreas and will prove useful in further studies of human pancreatic cells.</p>","PeriodicalId":77108,"journal":{"name":"Diabetes research (Edinburgh, Scotland)","volume":"20 3","pages":"61-71"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12518451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The response of regulatory peptides to moderate hypoglycaemia of short duration in type 1 (insulin-dependent) diabetes mellitus and in normal man.","authors":"G Tallroth, E Ryding, R Ekman, C D Agardh","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The changes in plasma gastrin-releasing peptide (GRP), arginine vasopressin (AVP), neuropeptide Y (NPY), corticotropin releasing hormone (CRH), galanin, ACTH, cortisol, delta sleep-inducing peptide (DSIP), adrenaline, noradrenaline and pancreatic polypeptide (PP) were measured after 5 and 15 minutes of acute insulin-induced moderate hypoglycaemia (2.0 mmol/l) in 10 patients with Type 1 diabetes mellitus with no autonomic neuropathy and in 10 healthy subjects. Plasma catecholamine and PP levels rose in both groups in response to hypoglycemia and the secretory response of ACTH was lower in the diabetic subjects (p < 0.01). GRP concentrations increased during hypoglycaemia (p < 0.01) while a reduction in AVP occurred at the start of hypoglycaemia (p < 0.001). The plasma AVP concentrations were higher in the diabetic group compared with those in the normal group (p < 0.05). The NPY concentrations were higher in the normal subjects (p < 0.05) but no change in the mean level occurred in either group during hypoglycaemia. No group differences or changes in mean plasma concentrations were found for galanin, DSIP and CRH. These observations support the view that regulatory peptides, if involved in glucose homeostasis, may rather have a modulatory effect than a direct action in restoring normoglycaemia.</p>","PeriodicalId":77108,"journal":{"name":"Diabetes research (Edinburgh, Scotland)","volume":"20 3","pages":"73-85"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12459690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolic effects of aldose reductase inhibition in diabetic man.","authors":"A J Krentz, S H Ellis, M Hardman, M Nattrass","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The metabolic effects of 52 weeks treatment with the aldose reductase inhibitor ponalrestat were examined in 32 diabetic patients (16 insulin treated) in a randomized, double-blind, placebo-controlled clinical trial. Twelve hour metabolic profiles were performed on two separate occasions in each patient (a) during a single-blind placebo run-in period and (b) after 52 weeks treatment with either ponalrestat 600 mg/day or matching placebo. No effects attributable to ponalrestat were evident in glucose, pyruvate, or alanine metabolism. A significant overall treatment effect was observed for lactate concentration (ponalrestat vs. placebo 12 h least square mean at 52 weeks: 1.35 vs. 1.65 mmol/l, p = 0.024). For glycerol (p = 0.018), non-esterified fatty acids (p = 0.003) and total ketone bodies (p = 0.045) there was evidence for a variation of treatment with time between the insulin treated and non-insulin treated patients, although no statistically significant overall treatment effects were observed for any metabolite. Fasting total ketone body concentration at 52 weeks was significantly elevated in the insulin-treated patients receiving ponalrestat (antilog LS mean: 0.12 vs. 0.01 mmol/l, p = 0.01). In conclusion, ponalrestat has no effect on glucose metabolism in diabetic patients. A potentially beneficial effect on lactate metabolism was accompanied by a minor ketogenic effect in insulin-treated patients.</p>","PeriodicalId":77108,"journal":{"name":"Diabetes research (Edinburgh, Scotland)","volume":"19 1","pages":"41-8"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12637363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C Bannai, M Yamazaki, Y Matsushima, K Kunika, M Itakura, Y Okuda, K Yamashita
{"title":"Amelioration of dermal lesions in streptozotocin-induced diabetic rats by aminoguanidine.","authors":"C Bannai, M Yamazaki, Y Matsushima, K Kunika, M Itakura, Y Okuda, K Yamashita","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>As aminoguanidine (AG) is known to prevent non-enzymatic glycosylation in various tissues, we have histologically and biochemically evaluated AG effects on the skin in control, SZ-diabetic and AG-treated (25 mg/kgbw/day, 10w) diabetic rats. HbA1c and plasma glucose levels in diabetic and AG-treated diabetic rats were maintained about two times higher than those in control rats during the 10 weeks of the experiment. Histological findings revealed that the dermis in diabetic rats was thin and edematous, associated with swelling and degeneration of collagen fibers. Necrobiotic changes were seen in the lower dermis. These changes were greatly improved in AG-treated diabetic rats. Skin glucose contents in diabetic and AG-treated diabetic rats were about 10 times higher than those in the controls, whereas there was no difference in the sorbitol contents between three groups. Dry weight of the skin and collagen content was well correlated (r = 0.9044) and collagen represented 78.0 +/- 2.3% of the dry weight. By SDS-PAGE analysis of cyanogen bromide digests it was shown that high molecular weight peptides were increased in diabetic rats, but were decreased in AG-treated diabetic rats. The mean of glycosaminoglycan (GAG) contents of diabetic skin was 54% of that in the controls (1.58 +/- 0.09 vs. 2.94 +/- 0.39 micrograms/mg dry weight, P < 0.0025), which increased significantly in AG-treated diabetic rats (1.75 +/- 0.07 microgram/mg dry weight, P < 0.01 vs. diabetic).(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77108,"journal":{"name":"Diabetes research (Edinburgh, Scotland)","volume":"20 4","pages":"87-95"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12517515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}