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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following the intravenous injection of streptozotocin into rats, postprandial hyperglycaemia was sustained from 24 hours over a subsequent period of some weeks and the rats were glucose intolerant. When streptozotocin was similarly injected into pertussis-sensitized or hydrocortisone treated rats, the postprandial hyperglycaemia observed at 24 hours did not persist, but showed a progressive decline until near normoglycaemia was obtained a week later. These animals manifested normal glucose tolerance one week after streptozotocin. Thus, a spontaneous recovery from streptozotocin-induced diabetes occurred under these conditions. This spontaneous recovery from diabetes was associated with hyperinsulinaemia in the fed state.
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PMID:Spontaneous recovery from streptozotocin-induced diabetes in rats pretreated with pertussis vaccine or hydrocortisone. 14 87

The purpose of the study was to determine the physiological actions of amylin, a novel 37-amino acid peptide isolated from pancreatic islet amyloid deposits. Our results showed that an infusion of amylin reduced fasting plasma insulin levels and impaired glucose tolerance in mice. Amylin significantly reduced insulin secretion in rat insulinoma cell lines (Rin m5F cells) that were stimulated by either isoproterenol and forskolin, but it did not affect insulin secretion stimulated by isobutyl-methylxanthine (IBMX) or dibutyryl cyclic-adenosine monophosphate (db-cAMP). Amylin also reduced cAMP levels in Rin m5F cells in response to isoproterenol, but did not affect cAMP levels in cells pretreated with pertussis toxin. These results suggest that the reduction of cAMP by amylin may be mediated through pertussis toxin-sensitive Gi proteins. Amylin significantly reduced basal and insulin-stimulated glycogen synthesis in rat primary cultured hepatocytes. Amylin stimulated basal and insulin-stimulated lipogenesis in hepatocytes. Amylin did not affect DNA synthesis in hepatocytes. These results suggest that amylin conducts dispersion actions on in vivo glucose metabolism in rat, and in vitro insulin secretion from Rin m5F cells and metabolism in rat hepatocytes.
Diabetes Res Clin Pract 1992 Jan
PMID:The effects of amylin on insulin secretion from Rin m5F cells and glycogen synthesis and lipogenesis in rat primary cultured hepatocytes. 131 71

It has been proposed that certain cytokines secreted by islet-infiltrating leukocytes may be involved in the pathogenesis of insulin-dependent diabetes mellitus by participation in beta-cell destruction. In the present study, the impact of various cytokines on replication and long-term insulin secretion by pancreatic beta-cells was investigated. To this end, fetal rat pancreatic islets containing a high fraction of beta-cells were exposed in culture for 1-3 days to interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interferon-alpha (IFN-alpha), and interleukin-6 (IL-6) at different concentrations. It was found that IL-1 beta markedly decreased beta-cell DNA synthesis during the first day of exposure, an effect that vanished after 2 days and was turned into a potent and dose-dependent stimulation by 3 days of exposure. At this latter time point, IL-1 beta also amplified the mitogenicity of growth hormone (GH) and 16.7 mM glucose. In contrast, basal as well as glucose- and GH-stimulated insulin secretion was consistently suppressed by IL-1 beta from days 1-3. IL-1 beta also lowered the islet adenosine 3',5'-cyclic monophosphate (cAMP) content at all time points studied. However, addition of the stimulatory cAMP analogue Sp-diastereomer of adenosine 3',5'-cyclic monophosphothioate or pertussis toxin, which themselves enhanced DNA synthesis and insulin secretion, failed to prevent the inhibitory actions of IL-1 beta on these parameters, making it unlikely that a decrease in cAMP is an important event in transduction of the inhibitory effects of the cytokine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effects of cytokines on long-term mitogenic and secretory responses of fetal rat pancreatic beta-cells. 132 36

We examined changes in guanosine triphosphate-dependent signal transduction mechanisms in the retina from the early stages of the streptozotocin-diabetic rat, a model for Type 1 (insulin-dependent) diabetes mellitus. Guanosine triphosphate binding, guanosine triphosphatase activity, and binding of (azido) guanosine triphosphate decreased significantly in the retina as early as 2 weeks after the induction of diabetes. The ability of guanosine triphosphate to inhibit forskolin-stimulatable adenyl cyclase was also abolished. These data suggest functional deterioration of G-proteins, especially Gi, in diabetic retina. Further studies using retinal rod outer segments revealed deterioration in light-sensitive, guanosine triphosphate-dependent functions of transducin in diabetic rats. Pertussis toxin-catalysed ADP ribosylation of the alpha subunit of transducin, a heterotrimeric G-protein of rod outer segments, was also reduced in diabetes. No functional effects were seen in purified subunits of transducin subjected to non-enzymatic glycation in vitro. On the other hand, incubation of non-diabetic rod outer segments with (12-0-tetradeconyl) phorbol-13-acetate, a protein kinase C agonist, in the presence of magnesium and adenosine triphosphate resulted in the reduction of guanosine triphosphate-binding and hydrolysis, thus indicating that protein kinase C may be involved in the regulation of these activities. The significance of these observations in the early visual abnormalities associated with diabetes is discussed.
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PMID:Functional alterations of G-proteins in diabetic rat retina: a possible explanation for the early visual abnormalities in diabetes mellitus. 132 50

The specific activity of Na(+)-K(+)-ATPase in the renal medulla and cortex of 50-day-old streptozotocin (STZ)-induced diabetic mice was increased 58% and 50%, respectively, as compared to controls. Km values of Na+ and K+ for this enzyme were unaltered, while that of ATP was decreased in diabetic mice. The Na(+)-K(+)-ATPase in control medulla and cortex was activated by both cholera and pertussis toxins, while this effect was abolished in diabetics. Since dibutyryl cAMP stimulates cortical Na(+)-K(+)-ATPase activity in control mice, the activation effect of cholera toxin on this enzyme might be due to its interaction with a Gs-protein and the persistent stimulation of adenylate cyclase activity, while the effect of pertussis toxin might be due to its masking of the inhibitory action of a Gi-protein on adenylate cyclase activity. However, the protein kinase C (PKC)-associated Na(+)-K(+)-ATPase might also be quiescent in diabetes, because the stimulating effect of phorbol 12,13-dibutyrate (PDBu) and phorbol 12-myristate 13-acetate (PMA) on this enzyme was abolished in diabetic cortex. In addition, nicardipine and ouabain were found to have differential effects on this enzyme derived from control and diabetic mice.
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PMID:Differentiation of renal Na(+)-K(+)-ATPase in control and streptozotocin-induced diabetic mice by G-protein acting toxins and phorbol esters. 132 74

All of the components of the neuropeptide vasoactive intestinal peptide (VIP) signal transduction system were underexpressed in rat prostatic membranes 6 weeks after streptozotocin-induced diabetes. Binding studies with [125I]VIP showed decreases of 86% and 62% in the binding capacity of the high and low affinity classes of VIP receptors in diabetes. Affinity labeling experiments indicated that the main form of VIP receptor was 51 kilodaltons in control rats and 45 kilodaltons in diabetic animals. The efficacy of VIP and forskolin in stimulation of adenylyl cyclase activity as well as the potentiating effect of GTP on VIP action were also reduced in diabetes, as was the expression of the alpha-subunit of the guanine nucleotide-binding regulatory proteins Gs and Gi (studied by ADP ribosylation with cholera and pertussis toxins). Gi function was lost in diabetes, as assessed with experiments on guanyl-5'-yl-imidodiphosphate potentiation of forskolin activity. These disturbances together with previous findings argue for VIP playing a role in the diabetic neuropathy of the genitourinary tract.
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PMID:The effect of streptozotocin diabetes on the vasoactive intestinal peptide receptor/effector system in membranes from rat ventral prostate. 132 26

G-proteins are important mediators of hormonal inhibition of insulin secretion. To characterize the pertussis toxin-sensitive substrates present in HIT cell membranes, we performed immunoblots with specific antisera and found evidence for the presence of Gi alpha 1, Gi alpha 2, Gi alpha 3, and three forms of Go alpha. We observed that pertussis toxin-sensitive substrates mediate all of the effects of SRIF, and a major portion of the effects of EPI, on insulin secretion from rat islets during static incubations. These results agree with our previously reported studies examining phasic glucose-induced insulin secretion from HIT cells. To ascertain whether inhibition of adenylate cyclase, presumably involving coupling of the catalytic subunit to Gi, may be a common mechanism for both hormones, we studied the effects of 8-bromo-cyclic AMP and found that this agent partially prevented the inhibitory effects of both hormones. We also observed that the inhibitory effects of SRIF and EPI on insulin were nonadditive, that both hormones were additive to nickel chloride during inhibition of insulin release, and that they noncompetitively inhibited glipizide-induced insulin secretion through pertussis toxin-sensitive mechanisms. Together, these results suggest that both hormones exert their effects on insulin secretion at multiple G-protein-regulated sites including adenylate cyclase and sites distal to the glipizide-binding site on the KATP channel.
Diabetes 1992 Nov
PMID:G-proteins and hormonal inhibition of insulin secretion from HIT-T15 cells and isolated rat islets. 138 67

Previous studies from our laboratory have suggested that diabetes-associated central nervous system abnormalities are characterized by progressive alterations of neurotransmitters and of transductional Gi/Go proteins. In this study, we have further characterized these abnormalities in the striatum of alloxan-diabetic rats by means of adenosine 5'-diphosphate (ADP)-ribosylation, and Western and Northern blotting techniques. Fourteen weeks after diabetes induction, pertussis-toxin (PTX) catalyzed ADP-ribosylation of Gi/Go proteins was markedly reduced in diabetic animals, as shown by a clear decrease of 32P-ADPribose incorporation into G protein alpha subunits. In agreement with our previous pharmacological studies that showed a reduction of Gi-mediated modulation of adenylate cyclase activity only at this stage of diabetes, no changes in PTX-mediated ADP-ribosylation were observed earlier (5-wk diabetes). Immunoblotting studies performed by using antibodies selectively raised against Gi-2, Go, and Gs proteins did not reveal any differences between control and diabetic animals at any stage of diabetes. Similarly, the mRNAs corresponding to the alpha subunits of Gi-2, Go, and Gs proteins did not show any marked changes in chronic diabetic rats with respect to control animals. It is therefore concluded that diabetes is associated with development of a time-related alteration of cerebral Gi/Go proteins and that this defect is not owing to gross changes in either content of G proteins or mRNA level, but probably reflects modifications of G protein's structure or physiological status affecting the coupling with membrane effector systems and the sensitivity to PTX.
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PMID:Diabetes-induced alterations of central nervous system G proteins. ADP-ribosylation, immunoreactivity, and gene-expression studies in rat striatum. 149 84

Streptozotocin-induced diabetes is accompanied by an increase in insulin-like immunoreactivity concentration in rat submandibular salivary glands. In this study we have examined whether, in normal state, maturation is accompanied by changes in insulin-like immunoreactivity concentration of rat submandibular salivary glands. Insulin-like immunoreactivity concentrations of submandibular salivary glands were significantly higher in 11 months old rats compared with 3.5 months old control animals. A pertussis toxin pretreatment provoked an increase in insulin-like immunoreactivity, suggesting that a pertussis toxin sensitive G-protein is involved in the regulation of insulin-like immunoreactivity in the rat submandibular salivary glands.
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PMID:Maturation and insulin-like immunoreactivity in rat submandibular salivary glands: possible implication of G regulatory proteins. 157 59

The early alterations of G-protein-dependent transductional mechanisms have been characterized in the retina of alloxan-treated diabetic rats. Five weeks after alloxan injection, pertussis toxin radiolabeling of Gi/Go proteins was markedly reduced in the retina of diabetic animals, suggesting either a reduced expression and/or the presence of some structural modification of these G-protein subtypes. The functional activity of Gs proteins, measured as stimulation of membrane adenylate cyclase by dopamine, did not seem to be impaired at this stage of the pathology; basal adenylate cyclase activity was indeed increased in diabetic rats, consistent with the observed reduction of Gi/Go inhibitory proteins. Such functional alterations of the cAMP producing system were causally related to diabetes induction, since they were reversed by treatment of diabetic animals with insulin. These results suggest that G-protein dependent transduction mechanisms are altered in the retina of diabetic animals, and that a defect of Gi/Go proteins could represent an early transductional damage in the development of diabetic retinopathy.
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PMID:Early alterations of Gi/Go protein-dependent transductional processes in the retina of diabetic animals. 165 57


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