International journal of experimental diabetes research最新文献

{"title":"Proinsulin C-peptide--a consensus statement.","authors":"A A Sima,&nbsp;G Grunberger,&nbsp;H Jörnvall,&nbsp;J Wahren","doi":"10.1155/edr.2001.145","DOIUrl":"https://doi.org/10.1155/edr.2001.145","url":null,"abstract":"<p><p>In recent years the physiological role of the proinsulin C-peptide has received increasing attention, focusing on the potential therapeutic value of C-peptide replacement in preventing and ameliorating type 1 diabetic complications. In order to consolidate these new data and to identify the immediate directions of C-peptide research and its clinical usefulness, an International Symposium was held in Detroit, Michigan, on October 20-21, 2000, under the auspices of the Wayne State University/Morris Hood Jr. Comprehensive Diabetes Center. In this communication, we review the cellular, physiological and clinical effects of C-peptide replacement in animal models and in patients with type 1 diabetes. Finally, recommendations are presented as to the most urgent studies that should be pursued to further establish the biological action of C-peptide and its therapeutic value.</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.2001.145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22055884","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":"Has C-peptide come of age?","authors":"A A Sima","doi":"10.1155/edr.2001.81","DOIUrl":"https://doi.org/10.1155/edr.2001.81","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":"https://sci-hub-pdf.com/10.1155/edr.2001.81","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22055885","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":"In vitro effect of fenugreek extracts on intestinal sodium-dependent glucose uptake and hepatic glycogen phosphorylase A.","authors":"M Al-Habori,&nbsp;A Raman,&nbsp;M J Lawrence,&nbsp;P Skett","doi":"10.1155/edr.2001.91","DOIUrl":"https://doi.org/10.1155/edr.2001.91","url":null,"abstract":"<p><p>Fenugreek (Trigonella foenum-graecum L. seed) is a food with traditional medicinal use in diabetes. Beneficial effects have been demonstrated in diabetic animals and both insulin-dependent and non-insulin-dependent diabetic subjects. Effects of a lipid extract A, crude ethanolic extract B, further sub-fractions of B (saponin-free C, saponin D and sapogenin E) and a gum fibre fraction F on intestinal sodium-dependent glucose uptake were investigated in vitro using rabbit intestinal brush border membrane vesicles. All fractions except A inhibited glucose-uptake at 0.33 and/or 3.3 mg/mL (p < 0.001). Greatest inhibition was observed with fractions D and E. Diosgenin and trigonelline (compounds reported in fenugreek) also inhibited glucose-uptake (IC50 values approximately 3 mg/ml, equivalent to 8 mM and 19 mM respectively) but did not account for the activity of the crude extracts. Fenugreek extracts had no effect on basal levels of glycogen phosphorylase a (HGPa) activity in rat hepatocyte suspensions. However fractions C and E caused a marginal but statistically significant inhibition (18.9 and 15.1% respectively, p < 0.05) of glucagon induction of this enzyme suggesting a glucagon-antagonist effect. Diosgenin (1.65 mg/ml; 4 mM) inhibited glucagon-induced HGPa activity by 20% (p < 0.05), and was more effective than trigonelline (non significant inhibition of 9.4% at 1.65 mg/ml, 10 mM).</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.2001.91","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22055837","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":"Functional enhancement of electrofusion-derived BRIN-BD11 insulin-secreting cells after implantation into diabetic mice.","authors":"E L Davies,&nbsp;Y H Abdel-Wahab,&nbsp;P R Flatt,&nbsp;C J Bailey","doi":"10.1155/edr.2001.29","DOIUrl":"https://doi.org/10.1155/edr.2001.29","url":null,"abstract":"<p><p>Electrofusion-derived BRIN-BD11 cells are glucose-sensitive insulin-secreting cells which provide an archetypal bioengineered surrogate beta-cell for insulin replacement therapy in diabetes mellitus. 5x10(6) BRIN-BD11 cells were implanted intraperitoneally into severely hyperglycaemic (>24 mmol/l) streptozotocin-induced insulin-treated diabetic athymic nude (nu/nu) mice. The implants reduced hyperglycaemia such that insulin injections were discontinued by 5-16 days (<17 mmol/l) and normoglycaemia (<9 mmol/l) was achieved by 7-20 days. Implanted cells were removed after 28 days and re-established in culture. After re-culture for 20 days, glucose-stimulated (16.7 mmol/l) insulin release was enhanced by 121% (p<0.001) compared to non-implanted cells. Insulin responses to glucagon-like peptide-1 (10(-9) mol/l), cholecystokinin-8 (10(-8) mol/l) and L-alanine (10 mmol/l) were increased by 32%, 31% and 68% respectively (p<0.05-0.01). Insulin content of the cells was 148% greater at 20 days after re-culture than before implantation (p<0.001), but basal insulin release (at 5.6 mmol/l glucose) was not changed. After re-culture for 40 days, insulin content declined to 68% of the content before implantation (p<0.01), although basal insulin release was unchanged. However, the insulin secretory responses to glucose, glucagon-like peptide-1, cholecystokinin-8 and L-alanine were decreased after 40 days of re-culture to 65%, 72%, 73% and 42% respectively of the values before implantation (p<0.05-0.01). The functional enhancement of electrofusion-derived surrogate beta-cells that were re-cultured for 20 days after implantation and restoration of normoglycaemia indicates that the in vivo environment could greatly assist beta-cell engineering approaches to therapy for 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.2001.29","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22055839","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":"Substrate-induced nuclear export and peripheral compartmentalization of hepatic glucokinase correlates with glycogen deposition.","authors":"T L Jetton,&nbsp;M Shiota,&nbsp;S M Knobel,&nbsp;D W Piston,&nbsp;A D Cherrington,&nbsp;M A Magnuson","doi":"10.1155/edr.2001.173","DOIUrl":"https://doi.org/10.1155/edr.2001.173","url":null,"abstract":"<p><p>Hepatic glucokinase (GK) is acutely regulated by binding to its nuclear-anchored regulatory protein (GKRP). Although GK release by GKRP is tightly coupled to the rate of glycogen synthesis, the nature of this association is obscure. To gain insight into this coupling mechanism under physiological stimulating conditions in primary rat hepatocytes, we analyzed the subcellular distribution of GK and GKRP with immunofluorescence, and glycogen deposition with glycogen cytochemical fluorescence, using confocal microscopy and quantitative image analysis. Following stimulation, a fraction of the GK signal translocated from the nucleus to the cytoplasm. The reduction in the nuclear to cytoplasmic ratio of GK, an index of nuclear export, correlated with a >50% increase in glycogen cytochemical fluorescence over a 60 min stimulation period. Furthermore, glycogen accumulation was initially deposited in a peripheral pattern in hepatocytes similar to that of GK. These data suggest that a compartmentalization exists of both active GK and the initial sites of glycogen deposition at the hepatocyte surface.</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.2001.173","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22056511","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":"Non insulin dependent diabetes in sand rat (Psammomys obesus) and production of collagen in cultured aortic smooth muscle cells. influence of insulin.","authors":"S A Bouguerra,&nbsp;M C Bourdillon,&nbsp;Y Dahmani,&nbsp;E Bekkhoucha","doi":"10.1155/edr.2001.37","DOIUrl":"https://doi.org/10.1155/edr.2001.37","url":null,"abstract":"<p><p>In this report, we have shown that the standard laboratory diet administered to Psammomys obesus (sand rat) from Beni Abbes in Algeria, induced a non-insulin dependent diabetes, characterised by increase of body weight (p<0.001) as well as hyperinsulinemia, hyperglycemia and hypercholesterolemia. In cultured aortic smooth muscle cells (SMC) of sand rats, type I and type III collagen biosynthesis and insulin effects, at low dose, on these parameters were investigated. In all experimental conditions of cultured SMC study, The alpha chains of type I collagen were analysed by immunoblotting in media and cells. Metabolic radiolabelling and Immunochemical procedures revealed that, in diabetic state, synthetic SMC (SMCs) actively produce type I and III collagen which are synthesised in the cells and secreted in the medium; type I collagen was predominant as compared with type III collagen. Diabetes enhanced the collagen synthesis. Low dose of Insulin added to the medium, during 48 h of incubation, induced a marked reduction in the synthesis of collagen types, especially type I collagen.</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.2001.37","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22055841","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":"Prevention of diabetes in the NOD mouse by intra-muscular injection of recombinant adeno-associated virus containing the preproinsulin II gene.","authors":"R M Jindal,&nbsp;M Karanam,&nbsp;R Shah","doi":"10.1155/edr.2001.129","DOIUrl":"https://doi.org/10.1155/edr.2001.129","url":null,"abstract":"<p><p>Using the Adeno-associated virus (AAV) as a gene delivery vehicle, we have constructed a recombinant vector containing the full length rat preproinsulin gene (vLP-1). Utilizing the well described non-obese diabetic (NOD) mouse model, an experimental group (n = 10) of animals were intramuscularly (i.m.) injected with 10(7) rAAV virions containing the insulin gene and compared to a mock-injected control group (n = 10). Blood glucose (glc) was then measured weekly for 16 weeks. Data showed that the experimental group contained 70% euglycemic animals (defined as glc<200 mg/dL) versus 10% of the control animals (P < .05) at 14 weeks. Mean weight in the treated group was greater than the untreated group. Insulin mRNA was detected at the injection site of all of the treated animals, but not controls. Complete destruction of islets was confirmed by histology ruling out the possibility of spontaneous reversal of insulinitis. We conclude that i.m. delivery of the insulin gene in the NOD mouse was able to prevent clinical DM up to 14 weeks in a majority of treated animals. Our experimental data suggests that gene therapy may be an alternative treatment for IDDM in the future.</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.2001.129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22055882","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":"Ebb and tide of glucokinase.","authors":"F M Matschinsky","doi":"10.1155/edr.2001.168","DOIUrl":"https://doi.org/10.1155/edr.2001.168","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":"https://sci-hub-pdf.com/10.1155/edr.2001.168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22056510","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":"Lessons from Animal Diabetes 8, 24–26 July 2001","authors":"Y. Kanazawa, S. Katayamá","doi":"10.1155/EDR.2001.247","DOIUrl":"https://doi.org/10.1155/EDR.2001.247","url":null,"abstract":"he 8th International Workshop on Lessons from Animal Diabetes was held July 24-26, 2001 at Nichidai Kaikan in Tokyo, the same venue where the 3rd Workshop took place in 1990. This issue of Experimental Diabetes Research is dedicated to providing coverage of the highlights of the lectures and communications presented at the workshop. The 8th LAD was organized jointly with the 15th annual meeting of Japan Association of Animal Diabetes Research (JAADR). JAADR is a research group initiated by Professor Yoshio Goto who established the famous GK rat model. There were over 200 participants about one half of them from Japan. Thus, the participants of 8th LAD had an opportunity to interact with many Japanese investigators. There was a novel session on \"Animal Models of Diabetes Established in Japan,\" which gave a special Japanese tone to the meeting. Twelve animal models were presented, many already widely known and others new that would get into international use soon. Among the important features was the 2nd Renold Memorial Lecture presented by Professor Eleazar Shafrir, entitled \"Molecular Background of Nutritionally Induced Insulin Resistance and Leading to Type 2 Diabetes from Animal Models to Humans\" (reprinted in this issue). We also had two plenary lectures by Doctor Palle Serup from Gentofte, Denmark on \"Pancreatic stem cells and islet cell differentiation\" and by Professor Takashi Kadowaki from the University of Tokyo on \"Molecular Pathogenesis of Type 2 diabetes in knockout mice models.\" LAD 8 comprised 4 symposia and 3 workshops in which we discussed the genetics and pathogenic mechanisms relevant to human type 1 and type 2 diabetes. We had 95 presentations, including short communications and posters not only related to pathogenesis of diabetes but also results of detailed mapping of genes, pathogenesis of complications and new therapeutic approaches. Abstracts of these communications appear in this volume. Listening and discussing these presentations, we felt that studies with animal models are opening new fields of diabetes research and significantly contribute to the understanding of pathogenesis of human diabetes and to the development of new therapeutic modalities. We thank all the participants for their contribution, especially those who came from outside Japan. We were able to make discussions as hot as the weather we had in Tokyo in July during the meeting.","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":"77030316","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":"Lack of Expression of Gp-130 Makes Pancreatic Beta Cell Lines Unresponsive to the IL-6 Family of Cytokines","authors":"G. Naselli, H. Deaizpurua, H. Thomas, A. M. Johnston, T. Kay","doi":"10.1155/EDR.2000.239","DOIUrl":"https://doi.org/10.1155/EDR.2000.239","url":null,"abstract":"Cytokine receptors from the IL-6 receptor family are comprised of ligand specific α chains and a common signalling chain, gp-130, which is also required for high affinity binding. A cDNA library generated from the β-TC3 SV40 T-antigen transformed insulinoma cell line was screened for members of this receptor family potentially relevant to both beta cell development and autoimmunity. Degenerate oligonucleotide primers to a consensus region of these receptors were used and the IL-11 receptor (α chain was identified. Despite confirmation of IL-11 receptor mRNA expression, iodinated bioactive IL-11 did not bind specifically to β-TC3 cells and gp-130-dependent cytokines did not elicit signalling events in beta cell lines. This was explained by absence of gp-130 protein or mRNA in the beta cell lines tested and in primary islets. We conclude from these resuits that the previously recognised effects of IL-6 family member cytokines on pancreatic islets must be indirect via other non-beta cells within the islet, rather than due to direct effects on beta cells themselves.","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":"81269736","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}