International journal of experimental diabetes research最新文献

{"title":"Human C-peptide dose dependently prevents early neuropathy in the BB/Wor-rat.","authors":"W Zhang,&nbsp;M Yorek,&nbsp;C R Pierson,&nbsp;Y Murakawa,&nbsp;A Breidenbach,&nbsp;A A Sima","doi":"10.1155/edr.2001.187","DOIUrl":"https://doi.org/10.1155/edr.2001.187","url":null,"abstract":"<p><p>In order to explore the neuroprotective and cross-species activities of C-peptide on type 1 diabetic neuropathy, spontaneously diabetic BB/W-rats were given increasing doses of human recombinant C-peptide (hrC-peptide). Diabetic rats received 10, 100, 500, or 1000 microg of hrC-peptide/kg body weight/day from onset of diabetes. After 2 months of hrC-peptide administration, 100 microg and greater doses completely prevented the nerve conduction defect, which was associated with a significant but incomplete prevention of neural Na+/K+-ATPase activity in diabetic rats with 500 microg or greater C-peptide replacement. Increasing doses of hrC-peptide showed increasing prevention of early structural abnormalities such as paranodal swelling and axonal degeneration and an increasing frequency of regenerating sural nerve fibers. We conclude that hrC-peptide exerts a dose dependent protection on type 1 diabetic neuropathy in rats and that this effect is probably mediated by the partially conserved sequence of the active C-terminal pentapeptide.</p>","PeriodicalId":14040,"journal":{"name":"International journal of experimental diabetes research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/edr.2001.187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22056512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of nateglinide on in vitro insulin secretion from rat pancreatic islets desensitized to sulfonylureas.","authors":"S Hu,&nbsp;S Wang,&nbsp;B E Dunning","doi":"10.1155/edr.2001.73","DOIUrl":"https://doi.org/10.1155/edr.2001.73","url":null,"abstract":"<p><p>Chronic exposure of pancreatic islets to sulfonylureas (SUs) is known to impair the ability of islets to respond to subsequent acute stimulation by SUs or glucose. Nateglinide (NAT) is a novel insulinotropic agent with a primarily site of action at beta-cell K(ATP) channels, which is common to the structurally diverse drugs like repaglinide (REP) and the SUs. Earlier studies on the kinetics, glucose-dependence and sensitivity to metabolic inhibitors of the interaction between NAT and K(ATP) channels suggested a distinct signaling pathways with NAT compared to REP, glyburide (GLY) or glimepiride (GLI). To obtain further evidence for this concept, the present study compared the insulin secretion in vitro from rat islets stimulated acutely by NAT, GLY, GLI or REP at equipotent concentrations during 1-hr static incubation following overnight treatment with GLY or tolbutamide (TOL). The islets fully retained the responsiveness to NAT stimulation after prolonged pretreatment with both SUs, while their acute response to REP, GLY, and GLI was markedly attenuated, confirming the desensitization of islets. The insulinotropic efficacy of NAT in islets desensitized to SUs may result from a distinct receptor/effector mechanism, which contributes to the unique pharmacological profile of NAT.</p>","PeriodicalId":14040,"journal":{"name":"International journal of experimental diabetes research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/edr.2001.73","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22055769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leptin and its relation to obesity and insulin in the SHR/N-corpulent rat, a model of type II diabetes mellitus.","authors":"M T Velasque,&nbsp;S J Bhathena,&nbsp;C T Hansen","doi":"10.1155/edr.2001.217","DOIUrl":"https://doi.org/10.1155/edr.2001.217","url":null,"abstract":"The spontaneously hypertensive/NIH-corpulent (SHR/N-cp) rat is a genetic animal model that exhibits obesity, metabolic features of hyperinsulinemia, hyperglycemia, and hyperlipidemia, which are characteristic of type II diabetes and mild hypertension. To determine the role of leptin, the protein product of the ob gene, in the development of obesity and diabetes in this model, we measured steady-state circulating levels of leptin in obese and lean SHR/N-cp rats and examined the relation between plasma leptin levels and metabolic variables at the stage of established obesity in these animals. Mean fasting plasma leptin concentration was 8-fold higher in obese than in lean rats (p<0.01). This was associated with a 6-fold elevation in plasma insulin in the obese group. Fasting levels of plasma glucose, cholesterol, and triglyceride were all significantly higher in obese rats than in lean controls. Spearman correlation analysis showed a significant positive correlation between plasma leptin concentration and body weight among the animals (r=0.73, p<0.01). Similarly, plasma insulin concentration was significantly correlated with BW in all animals (r=0.54, p<0.05). There was also a significant positive.correlation between plasma leptin and plasma insulin in the entire group (r=0.70, p<0.01). However, this relationship was significant only for lean rats but not for obese rats (r=0.59, p<0.05 for lean rats, and r=0.23, p=NS, for obese rats). Plasma leptin also correlated positively with fasting plasma glucose (r=0.75, p<0.05), total cholesterol (r=0.63, p<0.05), and triglyceride (r=0.67, p <0.05). The marked elevation of plasma leptin in obese SHR/N-cp rats suggests that obesity in this animal model is related to up-regulation of the ob gene. Circulating leptin appears to be one of the best biological markers of obesity and that hyperleptinemia is closely associated with several metabolic risk factors related to insulin resistance in the diabesity syndrome.","PeriodicalId":14040,"journal":{"name":"International journal of experimental diabetes research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/edr.2001.217","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22056516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of protein kinase C, PI3-kinase and tyrosine kinase in activation of MAP kinase by glucose and agonists of G-protein coupled receptors in INS-1 cells.","authors":"D Böcker,&nbsp;E J Verspohl","doi":"10.1155/edr.2001.233","DOIUrl":"https://doi.org/10.1155/edr.2001.233","url":null,"abstract":"<p><p>MAP (mitogen-activated protein) kinase (also called Erk 1/2) plays a crucial role in cell proliferation and differentiation. Its impact on secretory events is less well established. The interplay of protein kinase C (PKC), PI3-kinase and cellular tyrosine kinase with MAP kinase activity using inhibitors and compounds such as glucose, phorbol 12-myristate 13-acetate (PMA) and agonists of G-protein coupled receptors like gastrin releasing peptide (GRP), oxytocin (OT) and glucose-dependent insulinotropic peptide (GIP) was investigated in INS-1 cells, an insulin secreting cell line. MAP kinase activity was determined by using a peptide derived from the EGF receptor as a MAP kinase substrate and [32P]ATP. Glucose as well as GRP, OT and GIP exhibited a time-dependent increase in MAP kinase activity with a maximum at time point 2.5 min. All further experiments were performed using 2.5 min incubations. The flavone PD 098059 is known to bind to the inactive forms of MEK1 (MAPK/ERK-Kinase) thus preventing activation by upstream activators. 20 microM PD 098059 (IC50 = 5 microM) inhibited MAP kinase stimulated by either glucose, GRP, OT, GIP or PMA. Inhibiton (\"downregulation\") of PKC by a long term (22 h) pretreatment with 1 microM PMA did not influence MAP kinase activity when augmented by either of the above mentioned compound. To investigate whether PI3-kinase and cellular tyrosine kinase are involved in G-protein mediated effects on MAP kinase, inhibitors were used: 100 nM wortmannin (PI3-kinase inhibitor) reduced the effects of GRP, OT and GIP but not that of PMA; 100 microM genistein (tyrosine kinase inhibitor) inhibited the stimulatory effect of either above mentioned compound on MAP kinase activation. Inhibition of MAP kinase by 20 microM PD 098059 did not influence insulin secretion modulated by either compound (glucose, GRP, OT or GIP). [3H]Thymidine incorporation, however, was severely inhibited by PD 098059. Thus MAP kinase is important for INS-1 cell proliferation but not for its insulin secretory response with respect to major initiators and modulators of insulin release. The data indicate that MAP kinase is active and under the control of MAP kinase. PKC is upstream of a genistein-sensitive tyrosine kinase and probably downstream of a PI3-kinase in INS-1 cells.</p>","PeriodicalId":14040,"journal":{"name":"International journal of experimental diabetes research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/edr.2001.233","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22055878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diabetes in old male offspring of rat dams fed a reduced protein diet.","authors":"C J Petry,&nbsp;M W Dorling,&nbsp;D B Pawlak,&nbsp;S E Ozanne,&nbsp;C N Hales","doi":"10.1155/edr.2001.139","DOIUrl":"https://doi.org/10.1155/edr.2001.139","url":null,"abstract":"<p><p>Restricted fetal growth is associated with increased risk for the future development of Type 2 diabetes in humans. The study aim was to assess the glucose tolerance of old (seventeen months) male rats, which were growth restricted in early life due to maternal protein restriction during gestation and lactation. Rat mothers were fed diets containing either 20% or 8% protein and all offspring weaned onto a standard rat diet. In old-age fasting plasma glucose concentrations were significantly higher in the low protein offspring: 8.4 (1.3) mmol/l v. 5.3 (1.3) mmol/l (p = 0.005). Areas under the curves were increased by 67% for glucose (p = 0.01) and 81% for insulin (p = 0.01) in these rats in intravenous glucose tolerance tests, suggesting (a degree of) insulin resistance. These results show that early growth retardation due to maternal protein restriction leads to the development of diabetes in old male rat offspring. The diabetes is predominantly associated with insulin resistance.</p>","PeriodicalId":14040,"journal":{"name":"International journal of experimental diabetes research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/edr.2001.139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22055883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain-derived neurotrophic factor regulates energy expenditure through the central nervous system in obese diabetic mice.","authors":"T Nonomura,&nbsp;A Tsuchida,&nbsp;M Ono-Kishino,&nbsp;T Nakagawa,&nbsp;M Taiji,&nbsp;H Noguchi","doi":"10.1155/edr.2001.201","DOIUrl":"https://doi.org/10.1155/edr.2001.201","url":null,"abstract":"<p><p>It has been previously demonstrated that brain-derived neurotrophic factor (BDNF) regulates glucose metabolism and energy expenditure in rodent diabetic models such as C57BL/KsJ-lepr(db)/lepr(db) (db/db) mice. Central administration of BDNF has been found to reduce blood glucose in db/db mice, suggesting that BDNF acts through the central nervous system. In the present study we have expanded these investigations to explore the effect of central administration of BDNF on energy metabolism. Intracerebroventricular administration of BDNF lowered blood glucose and increased pancreatic insulin content of db/db mice compared with vehicle-treated pellet pair-fed db/db mice. While body temperatures of the pellet pair-fed db/db mice given vehicle were reduced because of restricted food supply in this pair-feeding condition, BDNF treatment remarkably alleviated the reduction of body temperature suggesting the enhancement of thermogenesis. BDNF enhanced norepinephrine turnover and increased uncoupling protein-1 mRNA expression in the interscapular brown adipose tissue. Our evidence indicates that BDNF activates the sympathetic nervous system via the central nervous system and regulates energy expenditure in obese diabetic animals.</p>","PeriodicalId":14040,"journal":{"name":"International journal of experimental diabetes research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/edr.2001.201","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22056514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Albert Renold Memorial Lecture: Molecular Background of Nutritionally Induced Insulin Resistance Leading to Type 2 Diabetes – From Animal Models to Humans","authors":"E. Shafrir,","doi":"10.1155/EDR.2001.299","DOIUrl":"https://doi.org/10.1155/EDR.2001.299","url":null,"abstract":"Albert Renold strived to gain insight into the abnormalities of human diabetes by defining the pathophysiology of the disease peculiar to a given animal. He investigated the Israeli desert-derived spiny mice (Acomys cahirinus), which became obese on fat-rich seed diet. After a few months hyperplasia and hypertrophy of β-cells occurred leading to a sudden rupture, insulin loss and ketosis. Spiny mice were low insulin responders, which is probably a characteristic of certain desert animals, protecting against insulin oversecretion when placed on an abundant diet. We have compared the response to overstimulation of several mutant diabetic species and nutritionally induced nonmutant animals when placed on affluent diet. Some endowed with resilient β-cells sustain long-lasting oversecretion, compensating for the insulin resistance, without lapsing into overt diabetes. Some with labile beta cells exhibit apoptosis and lose their capacity of coping with insulin resistance after a relatively short period. The wide spectrum of response to insulin resistance among different diabetes prone species seems to represent the varying response of human beta cells among the populations. In search for the molecular background of insulin resistance resulting from overnutrition we have studied the Israeli desert gerbil Psammomys obesus (sand rat), which progresses through hyperinsulinemia, followed by hyperglycemia and irreversible beta cell loss. Insulin resistance was found to be the outcome of reduced activation of muscle insulin receptor tyrosine kinase by insulin, in association with diminished GLUT4 protein and DNA content and overexpression of PKC isoenzymes, notably of PKCε. This overexpression and translocation to the membrane was discernible even prior to hyperinsulinemia and may reflect the propensity to diabetes in nondiabetic species and represent a marker for preventive action. By promoting the phosphorylation of serine/threonine residues on certain proteins of the insulin signaling pathway, PKCε exerts a negative feedback on insulin action. PKCε was also found to attenuate the activity of PKB and to promote the degradation of insulin receptor, as determined by co-incubation in HEK 293 cells. PKCε overexpression was related to the rise in muscle diacylglycerol and lipid content, which are prevalent on lascivious nutrition especially if fat-rich. Thus, Psammomys illustrates the probable antecedents of the development of worldwide diabetes epidemic in human populations emerging from food scarcity to nutritional affluence, inappriopriate to their metabolic capacity.","PeriodicalId":14040,"journal":{"name":"International journal of experimental diabetes research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88417053","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":"Abstracts of the 3rd Annual International Motor City Diabetes Symposium","authors":"Donald F. Stenier","doi":"10.1155/EDR.2001.153","DOIUrl":"https://doi.org/10.1155/EDR.2001.153","url":null,"abstract":"","PeriodicalId":14040,"journal":{"name":"International journal of experimental diabetes research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79264713","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":"High insulin requirements and poor metabolic control do not modify the expression, regulation and PKC mediated activation of the p21ras pathway in PBMC from type II diabetic patients.","authors":"M J Rapoport,&nbsp;O Levi,&nbsp;M Weiss,&nbsp;A Buchs,&nbsp;Y Ramot,&nbsp;D Aharoni,&nbsp;A Mor,&nbsp;G Elberg,&nbsp;Y Katz,&nbsp;J Weissgarten","doi":"10.1155/edr.2001.47","DOIUrl":"https://doi.org/10.1155/edr.2001.47","url":null,"abstract":"<p><strong>Aims: </strong>To asses whether clinically severe insulin resistance and poor metabolic control in patients with type 11 diabetes are associated with aberrant expression or function of the p21ras pathway.</p><p><strong>Methods: </strong>We examined the expression and function of the p21ras pathway in resting and activated PBMC from 10 insulin treated patients with type II diabetes characterized by high insulin requirements and poor metabolic control (IR group) and 10 age and sex matched well controlled patients treated by diet alone or oral hypoglycemic medications (WC group).</p><p><strong>Results: </strong>Levels of p21ras and its regulatory elements: p21rasGAP and hSOS1, were comparable in the two groups. The induced activities of p21ras and its associated down-stream regulatory enzyme MAP-kinase following TPA stimulation were also comparable in the IR and WC patients.</p><p><strong>Conclusions: </strong>Taken together, these data indicate that clinically significant severe insulin resistance does not modify the expression, regulation and activation of p21ras pathway in PBMC of patients with type II diabetes.</p>","PeriodicalId":14040,"journal":{"name":"International journal of experimental diabetes research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/edr.2001.47","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22055842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin and glucagon impairments in relation with islet cells morphological modifications following long term pancreatic duct ligation in the rabbit--a model of non-insulin-dependent diabetes.","authors":"J Catala,&nbsp;M Daumas,&nbsp;A P Chanh,&nbsp;B Lasserre,&nbsp;E Hollande","doi":"10.1155/edr.2001.101","DOIUrl":"https://doi.org/10.1155/edr.2001.101","url":null,"abstract":"<p><p>Plasma levels of glucose, insulin and glucagon were measured at various time intervals after pancreatic duct ligation (PDL) in rabbits. Two hyperglycemic periods were observed: one between 15-90 days (peak at 30 days of 15.1 +/- 1.2 mmol/l, p < 0.01), and the other at 450 days (11.2 +/- 0.5 mmol/l, p < 0.02). The first hyperglycemic episode was significantly correlated with both hypoinsulinemia (41.8 +/- 8 pmol/l, r = -0.94, p < 0.01) and hyperglucagonemia (232 +/- 21 ng/l, r = 0.95, p < 0.01). However, the late hyperglycemic phase (450 days), which was not accompanied by hypoinsulinemia, was observed after the hyperglucagonemia (390 days) produced by abundant immunostained A-cells giving rise to a 3-fold increase in pancreatic glucagon stores. The insulin and glucagon responses to glucose loading at 180, 270 and 450 days reflected the insensitivity of B- and A-cells to glucose. The PDL rabbit model with chronic and severe glycemic disorders due to the predominant role of glucagon mimicked key features of the NIDDM syndrome secondary to exocrine disease.</p>","PeriodicalId":14040,"journal":{"name":"International journal of experimental diabetes research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/edr.2001.101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22055879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}