Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The frequency of secondary failure to oral hypoglycaemic agents (OHA) in patients with non-insulin dependent diabetes (NIDDM) is still unknown, despite more than 30 years of use of OHA. The term secondary failure should be limited to patients who, despite maximal dosages of OHA and despite full compliance with diet and therapy, are no longer controlled and require insulin to obtain an acceptable glucose metabolism. We evaluated 248 out-patients, either on OHA, or on insulin because of poor metabolic control with OHA, in order to assess duration of treatment with OHA since diagnosis, by means of actuarial curves (Mantel-Cox test). Patients with low relative body weight (RBW less than or equal to 100) experienced secondary failure earlier and more often than obese patients (RBW greater than 120) or overweight (RBW 101-120) patients. In 66 of the above out-patients, 33 OHA-treated and 33 insulin-treated, matched for age at onset and duration of disease, islet-cell-antibodies (ICA) and C-peptide release at fasting, 6 min after i.v. glucagon and post prandially were evaluated. Only among lean and overweight patients, was C-peptide release significantly lower in insulin-treated than in OHA-treated patients; differences disappeared in obese patients. ICA were found in only 7 patients (10.6%). HLA phenotype was different from that of healthy blood donors for the loci HLA B5, B13, CW4, with no differences between OHA-treated and insulin-treated patients. These data indicate that secondary failure is more frequent in lean patients with NIDDM, and is related to reduced insulin release.
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PMID:Secondary failure to oral hypoglycaemic agents in non-obese patients with non-insulin-dependent diabetes is related to reduced insulin release. 266 Dec 81

Pancreatic AR42J cells are derived from acinar cells and express both exocrine and neuroendocrine properties. We have recently shown that these cells convert into insulin-producing cells in vitro after treatment with activin A and betacellulin. Here, we investigated the effect of hepatocyte growth factor (HGF) in those cells. When AR42J cells were incubated with HGF, DNA synthesis was attenuated, and the amylase content was reduced in a concentration-dependent manner. HGF-treated cells extended processes, but bundle formation was not observed using an antibody against tubulin. Reverse both insulin and pancreatic polypeptide (PP) were expressed in HGF-treated, but not naive, AR42J cells. Immunocytochemical analysis indicated that approximately 3% of the HGF-treated cells were stained with antiinsulin antibody, and some were also stained with anti-PP antibody. When AR42J cells were exposed to a combination of activin A and HGF, cells extended longer processes, and over 10% of them were stained with antiinsulin antibody. In these cells, messenger RNAs for insulin, PP, glucose transporter 2, and glucokinase, but not those for glucagon or somatostatin, were expressed. A subclone of AR42J cells, AR42J-B13, was obtained. Most of the AR42J-B13 cells converted to insulin-producing cells after the incubation with activin A and HGF. Insulin secretion was augmented by tolbutamide, depolarizing concentrations of potassium, carbachol, and glucagon-like peptide-1 in these cells. These results indicate that HGF reduces the acinar cell-like property of AR42J cells and converts them into insulin-producing cells. The effect of HGF was markedly enhanced by activin A.
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PMID:Formation of insulin-producing cells from pancreatic acinar AR42J cells by hepatocyte growth factor. 875 73

The wood frog Rana sylvatica utilises glucose, derived from hepatic glycogen, as a cryoprotectant in order to survive freezing during winter hibernation, and glycogenolysis is initiated by hormonal and/or neural stimuli. The primary structure of insulin was determined from R. sylvatica and from two species of freeze-intolerant Ranid frogs R. catesbeiana (American bullfrog) and R. ridibunda (European green frog). All three insulins contain a dipeptide (Lys-Pro) extension to the N-terminus of the A-chain. The amino acid sequences of insulins from R. catesbeiana and R. ridibunda differ by only one residue (Asp for Glu at B21) but R. sylvatica insulin differs from R. catesbeiana insulin at A12 (Thr-->Met), A23 (Asn-->Ser), B5 (Tyr-->His) and B13 (Glu-->Asp). The residue at A23 (corresponding to A21 in human insulin) has been otherwise fully conserved during evolution and the residue at B13 has been strongly conserved in tetrapods. Insulin isolated from specimens of R. sylvatica that had been frozen for 24 h and from control animals that had not been frozen had the same structure, showing that freezing did not alter the pathway of post-translational processing of proinsulin. R. sylvatica glucagon was isolated in two molecular forms. Glucagon-29 was identical to R. catesbeiana glucagon-29 and contains only one amino acid substitution (Thr-->Ser) compared with human glucagon. Glucagon-36 represents glucagon-29 extended from its C-terminus by Lys-Arg-Ser-Gly-Gly-Ile-Ser and is identical to R. catesbeiana glucagon-36. We speculate that selective changes in the structure of the insulin molecule may contribute to the anomalous regulation of glycogen phosphorylase in the wood frog.
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PMID:Freeze tolerance in the wood frog Rana sylvatica is associated with unusual structural features in insulin but not in glucagon. 980 58

AR42J is an exocrine pancreatic cell line that has been reported to differentiate towards an endocrine phenotype when stimulated with various growth factors, such as activin A, hepatocyte growth factor (HGF), betacellulin or glucagon-like peptide 1. In our experiments, AR42J-B13 cells differentiated morphologically in response to the growth factor treatment as reported previously. However, they failed to express the insulin gene. We found that the cells did not express several transcription factors known to be found in the beta-cell, including Nkx6.1, isl-1, Pax4 and Pax6. In addition, the mRNA level for pdx-1 and Nkx2.2 were very low in comparison to the insulinoma cell lines INS-1 and RINm5F. However, some transcription factors typically found in beta-cells and neuroendocrine cells were expressed also in the AR42J-B13 cells. These included BETA2/NeuroD, HNF1alpha, C/EBPbeta and IA-1. Unlike the insulinoma cells, AR42J cells expressed the exocrine transcription factor p48. In order to induce endocrine differentiation, we transfected the AR42J-B13 cells with the full length cDNAs of isl-1, Nkx6.1, Nkx2.2 and pdx-1 under the control of the CMV promoter, both separately and in combinations. The expression of Nkx2.2 led consistently to the appearance of pancreatic polypeptide but not insulin, glucagon or somatostatin mRNA. The PP mRNA expression in Nkx2.2 cDNA transfected cells was independent of the growth factor treatment used for differentiating AR42J cells. In conclusion, the AR42J-B13 line possesses some features of a pancreatic neuroendocrine cell. However, we were unable to confirm the capacity of these cells to differentiate into insulin-producing cells. Our results indicate that Nkx2.2 plays a role in the transcriptional regulation of PP expression.
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PMID:Transcription factor expression and hormone production in pancreatic AR42J cells. 1094 Apr 82

The AR42J-B13 rat pancreatic acinar cell line was used to identify pancreatic transcription factors and exogenous growth factors (GFs) that might facilitate the reprogramming of exocrine cells into islets. Adenoviruses were used to induce exogenous expression of the pancreatic transcription factors (TFs) Pdx1, MafA, Ngn3 and Pax4. Individually Pdx1, MafA and Pax4 had no effect on the expression of endocrine markers, whilst adeno-Ngn3 on its own increased the expression of Pax4, Ngn3 and NeuroD. In combination the four TFs had a significant effect on the expression of insulin 1 and 2 that was associated with a change in cell morphology from a rounded to a spindle-like shape. Amongst a range of growth factors, Betacellulin and Nicotinamide were shown to enhance the effects of the four TFs. The presence of adeno-Pax4 in the differentiation cocktail was important in limiting the expression of glucagon and in generating glucose sensitive insulin secretion. Further experiments asked whether the adenoviral TFs could be replaced by protein transduction domain (PTD)-containing TFs. The results showed that the PTD-TFs could mimic in part the effects of the adeno-TFs, but the resultant cells did not undergo the important morphological change associated with differentiation to endocrine lineages and levels of endogenous markers were very much lower. In summary, the results describe a cocktail of four TFs and two GFs that can be used to induce formation of glucose sensitive insulin secreting cells from ARJ42 cells, and demonstrate that it would be difficult to replace adenoviral transduction with PTD-TFS.
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PMID:Efficient differentiation of AR42J cells towards insulin-producing cells using pancreatic transcription factors in combination with growth factors. 2242 91