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

Protective effect of pertussis vaccine (PV) against the development of insulin-dependent diabetes (IDD) induced by streptozotocin (STZ) in young CD-1 male mice were studied. When PV at a dose of 1.2 X 10(10) microorganism was administered on -10, 0, or +4 d relative to a single injection of STZ (60 mg/kg body wt) on d 0, it completely aborted the development of IDD after 140 d. When PV was given on +30 d after STZ injection and followed by PV booster injections, 66% of mice reverted to normoglycemic state. Intact islet cells in the pancreas were confirmed by histologic findings and normal plasma insulin values. The effect of PV was compared with that of boiled PV in another model of IDD induced by multiple injections of STZ (40 mg/kg for five doses). In this model, 60% of mice either remained or reverted to normoglycemic state with PV and booster injections whereas boiled PV protected 40% of mice from developing IDD. The protective effect appeared to reside in the biologic property of both pertussigen and endotoxin of Bordetella pertussis.
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PMID:The effect of pertussis vaccine on the insulin-dependent diabetes induced by streptozotocin in mice. 636 24

We have previously determined the presence of muscarinic receptors and the expression of several G proteins in homogenates and myelin fractions from rat sciatic nerves. In the present study we investigated whether changes in several signal transduction pathways in peripheral nerves might be responsible for some of the biochemical abnormalities (e.g., phosphoinositide metabolism) present in sciatic nerves from streptozotocin-induced diabetic rats. Sciatic nerves from 5 week diabetic rats that were prelabelled with [3H]-myo-inositol displayed a significant increase in the basal release of inositol mono- and bis-phosphate, while carbamylcholine-stimulated release was significantly smaller. Basal- and forskolin-stimulated adenylyl cyclase activity was significantly decreased in sciatic nerve homogenates from diabetic animals. However, we were unable to detect any significant differences in the levels of cAMP in intact nerves or in nerve segments that were incubated in the presence or absence of forskolin. ADP-ribosylation experiments showed that in sciatic nerves from experimentally diabetic rats there was a significant increase in the ADP-ribosylation catalyzed by cholera and pertussis toxins. Measurements of the levels of alpha-subunits of G proteins revealed that the expression of Gq/11 alpha, Gs alpha, and Gi-3 alpha was increased by 30 to 50%. These results indicate that during the course of experimental diabetes, peripheral nerves exhibit an abnormal production of inositol phosphates and cAMP, together with an abnormal expression and/or function of G proteins. One of the consequences of such alterations is the diminished release of inositol phosphates triggered by muscarinic agonists in diabetic sciatic nerves.
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PMID:Signal transduction alterations in peripheral nerves from streptozotocin-induced diabetic rats. 747 83

Inhibition of insulin secretion by galanin is pertussis toxin (PTX) sensitive, suggesting the activation of one or more heterotrimeric (alpha, beta, gamma) G-proteins (Gi/Go). Multiple effectors, including the K+ATP and L-type Ca2+ channels, adenylyl cyclase, and an as yet unidentified system at a site close to exocytosis, are modulated by galanin. Therefore, it is necessary to delineate the particular G-proteins activated by the galanin receptor as a first step to understanding its net cellular response. During specific conditions, cholera toxin (CTX) can ADP-ribosylate the alpha i/alpha o-subunits of the PTX-sensitive substrates but only during receptor/G-protein interaction. Therefore, we used CTX-catalyzed ADP ribosylation to identify galanin receptor-associated G-protein alpha-subunits in RINm5F cells. Galanin enhanced the ADP ribosylation of membrane proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in two bands at 39,000 and 42,000 M(r). This labeling was blocked in membranes prepared from PTX-treated cells, enhanced by Mg2+, and showed a biphasic dependence on exogenous guanine nucleotides. Identification of the CTX ADP-ribosylated G-proteins by immunoprecipitation with selective antisera indicate activation by the galanin receptor of alpha i1 and alpha i3, which have the same mobility on SDS-PAGE (42,000 M(r)), and alpha i2 (39,000 M(r)). These studies provide evidence for the activation of multiple G-proteins by receptors for galanin in RINm5F cells.
Diabetes 1994 Jan
PMID:ADP ribosylation by cholera toxin identifies three G-proteins that are activated by the galanin receptor. Studies with RINm5F cell membranes. 750 45

Morphological analysis of hormone content and functional assessment of hormone secretion were conducted in beta TC-6 cells, an insulin-secreting cell line derived from transgenic mice expressing the large T-antigen of simian virus 40 (SV40) in pancreatic beta-cells. We observed by immunohistochemistry and confocal microscopy that beta TC-6 cells contain abundant insulin and small amounts of glucagon and somatostatin (SRIF). Glucagon usually co-localized with insulin, whereas cells containing SRIF did not contain insulin or glucagon. Static incubation and perifusion experiments demonstrated that beta TC-6 cells at passage 30-45 secrete insulin in response to glucose. In static incubations, maximal stimulation was achieved for glucose concentrations > 2.8 mmol/l glucose, and the half-maximal effect was observed at 0.5 mmol/l. Maximal stimulation was four times greater than HIT-T15 cells at passage 72-81, although HIT cells had a greater response over their basal levels. The magnitude of the insulin response to glucose in perifusion was 1,734 +/- 384 pmol.l-1. min and was 4.6-fold greater in the presence of 3-isobutyl-1-methylxanthine. Low amounts of glucagon were released in response to amino acids. Epinephrine (EPI), and to a lesser extent SRIF, inhibited phasic glucose-induced insulin secretion. A major portion of these inhibitory effects was mediated by pertussis toxin-sensitive substrates. Immunoblots detected the presence of the G-proteins Gi alpha 2, Gi alpha 3, and Go alpha 2. These results indicate that beta TC-6 cells are a glucose-responsive cell line in which insulin exocytosis is physiologically regulated by EPI and SRIF through Gi/Go-mediated mechanisms.
Diabetes 1995 Mar
PMID:Morphological and functional characterization of beta TC-6 cells--an insulin-secreting cell line derived from transgenic mice. 753 32

Inhibition of adenylyl cyclase activity is one of at least four mechanisms by which the neuropeptide galanin inhibits insulin secretion from pancreatic beta-cells. In a membrane preparation of the insulin-secreting cell line RINm5F, a maximally effective concentration of galanin inhibited forskolin-stimulated adenylyl cyclase activity by 30%. Pretreatment of the cells with pertussis toxin abolished the inhibitory effect of galanin, indicating the involvement of Gi or Go guanine nucleotide binding proteins (G-proteins). Because galanin receptors interact with four G-proteins (Gi1, Gi2, Gi3, and Go1), any or all of these may inhibit adenylyl cyclase. Therefore, to identify the G-protein(s) involved, antibodies raised against various G-protein alpha-subunits were used to block the inhibition of forskolin-stimulated adenylyl cyclase activity by galanin in RINm5F membrane preparations. Antisera AS/7 and EC/2, specific for G alpha i1/alpha i2 and G alpha i3, respectively, were able to significantly attenuate the inhibitory effect of galanin, whereas antisera specific for Go proteins were not. The use of additional antisera specific for the various subtypes of Gi proteins indicated that Gi2 and Gi3, but not Gi1, are involved. Simultaneous application of antisera AS/7 and EC/2 resulted in a greater attenuation of the effect of galanin than application of either antiserum alone. Thus, galanin inhibition of adenylyl cyclase activity in these cells is selectively mediated by two inhibitory G-proteins, Gi2 and Gi3.
Diabetes 1995 Apr
PMID:Gi2 and Gi3 proteins mediate the inhibition of adenylyl cyclase by galanin in the RINm5F cell. 753 66

Insulin treatment of platelets is associated with increased prostaglandin E1-stimulated adenylyl cyclase activity and decreased platelet aggregation. Because non-insulin dependent (Type II) diabetes mellitus is associated with hyperinsulinemia, we sought to determine the effect of insulin treatment in vivo and in vitro upon stimulation of platelet adenylyl cyclase by prostaglandin E1. Incubation of platelet-rich plasma obtained from normal subjects with 2 microM prostaglandin E1 resulted in a 16-fold increase in cAMP accumulation. Pre-incubation of platelet-rich plasma with 0.7 nM insulin resulted in a 62% increase in prostaglandin E1 (2 microM)-stimulated cAMP accumulation (p < 0.005). Pretreatment of platelets with cholera toxin prior to incubation with insulin had no effect on subsequent prostaglandin E1-stimulated cAMP accumulation. By contrast, pretreatment of platelets with pertussis toxin prior to incubation with insulin resulted in a nearly 2-fold increase in prostaglandin E1-stimulated cAMP accumulation (p < 0.005). To determine whether platelets exposed in vivo to elevated concentrations of insulin would show similar responses, we isolated platelet-rich plasma from subjects before and after a 120 minute euglycemic clamp study in which insulin was infused (40 mU m-2min-1) intravenously. Patients who underwent the euglycemic clamp study achieved steady state serum levels on insulin of 0.70 +/- 0.19 pmol/ml. Platelets obtained after insulin infusion had a 65% increase in prostaglandin E1-stimulated cAMP. Our results indicate that serum levels of insulin that are common in patients with type II diabetes mellitus can increase the sensitivity of platelet adenylyl cyclase to stimulation by prostaglandin E1.
Diabetes Res 1994
PMID:The effects of in vitro and in vivo exposure to insulin upon prostaglandin E1 stimulation of platelet adenylate cyclase activity in healthy subjects. 764 95

Previously, we have demonstrated that somatostatin mediates all of its inhibitory effects on glucose-induced insulin secretion from the HIT-T15 cell through pertussis toxin-sensitive G-proteins and that the membrane fraction of this clonal line of pancreatic beta-cells contains six such proteins: G(i) alpha 1, G(i) alpha 2, G(i) alpha 3, and three forms of G(o) alpha. To determine the specificity of somatostatin receptor-G-protein coupling in HIT-T15 cells, we examined the ability of antisera specific for the COOH-terminus of G alpha subtypes to inhibit somatostatin-induced augmentation of membrane GTPase activity. GTPase activity increased in membranes as a function of GTP. At all concentrations of GTP studied, 1 mumol/l somatostatin stimulated GTPase activity. Pertussis-toxin pretreatment prevented the effects of somatostatin. Antisera selective for G(o) alpha subtypes reduced the effects of somatostatin on GTPase activity (GTPase activity in absence of antisera, 125 +/- 3% of control; in the presence of antisera 976, 110 +/- 2% of control; n = 13, P < 0.001), whereas antisera directed against G(i) alpha 1, G(i) alpha 2, G(i) alpha 3, and Gs alpha were without effect. Somatostatin also significantly prevented cyclic AMP accumulation during perifusion with 11.1 mmol/l glucose through a pertussis toxin-sensitive mechanism. These data indicate that the somatostatin receptor couples to G(o) alpha in the HIT-T15 cell and suggest that G(o) alpha may link somatostatin to cyclic AMP metabolism in pancreatic beta-cells.
Diabetes 1995 Jan
PMID:Somatostatin selectively couples to G(o) alpha in HIT-T15 cells. 781 19

The development of insulin-dependent diabetes mellitus is thought to be related to environmental trigger factors acting upon a background of genetic predisposition to the disease. Viral infections, toxins, and dietary factors are being considered as trigger factors. The authors studied the relationship of the development of diabetes from birth up to 15 years of age to the type of feeding in infancy, childhood infections, and vaccination among 55 patients attending Endocrinology Clinics of the Ethio-Swedish Children's and Tikur Anbessa Hospitals over the period January 1990 to December 1991. 74 unaffected siblings and 107 unrelated individuals were included as controls. No significant difference was found in relation to type of feeding up to the ages of three, six, and twelve months or older between patients and unaffected siblings. Histories of measles, chicken pox, and whooping cough were equally distributed between the two groups. The introduction of bottle-feeding, however, was significantly more frequent among unrelated controls at three months and six months of age. The use of cow's milk and other formulas in bottle-feeding showed a significant negative association with the development of diabetes. An history of vaccination against tuberculosis, measles, diphtheria, pertussis, tetanus, and polio was significantly more common among unrelated controls than diabetics. There was no significant difference in family history of diabetes in first degree relatives, parental education, and level of income between diabetics and unrelated controls. The authors suggest that more extensive studies are warranted.
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PMID:The relation of early nutrition, infections and socio-economic factors to the development of childhood diabetes. 783 52

Recent additions to the immunization schedule include acellular pertussis vaccine, and hepatitis B vaccine for all infants and selected adolescents. The third dose of OPV is recommended at 6 months of age and the first dose of MMR vaccine at 12 to 15 months. A new vaccine against Haemophilus influenzae type b has been licensed. Children aged 6 months and older with asthma, diabetes, or heart disease should receive influenza vaccine. Children aged 2 years and older with asplenia, immunosuppression, and nephrotic syndrome may be candidates for pneumococcal immunization.
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PMID:Childhood immunization guidelines: current and future. 785 58

The insulin secreting B cell is fitted with the two types of purinergic receptors: P2 (for ATP and/or ADP) and P1 (for adenosine). The activation of P2 purinoceptors by ATP or ADP evokes a biphasic stimulation of insulin secretion from isolated perfused rat pancreas; this stimulation is dose-dependent between 10(-6) and 10(-4) M. Non hydrolysable structural analogues are also effective, and the relative potency of various agonists (2-methylthio ATP >> ATP = ADP = alpha, beta-methylene ATP >> AMP) gave evidence for a P2y purinoceptor subtype. Proposed mechanisms include both an increased Ca2+ uptake and an increased intracellular Ca2+ mobilization via the hydrolysis of polyphosphoinositides. ATP (or ADP) potentiates physiological insulin-secreting agents (glucose and acetylcholine) and P2 purinoceptors could play a physiological role in the stimulation of insulin secretion. The activation of P1 purinoceptors (adenosine receptors) decreases insulin secretion. Using structural analogues of adenosine, the receptor was characterized as an A1 subtype; it is coupled to a pertussis toxin sensitive G protein and it inhibits adenylate cyclase. It is of physiological relevance that the B cell has the two types of purinoceptors with opposite effects. Recently, a metabolically stable structural analogue of ADP, adenosine-5'-0-(2-thiodiphosphate) or ADP beta S, has been described as a potent secretory agent, effective at nanomolar concentrations on isolated perfused rat pancreas. In vivo, this substance is able to increase insulin secretion and to improve glucose tolerance after IV administration in rats and oral administration in dogs. Furthermore in streptozotocin-induced diabetes. ADP beta S retains its insulin secreting effects. These results suggest that P2y purinoceptors could be a new target for antidiabetic drugs.
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PMID:Purinergic receptors on insulin-secreting cells. 802 Aug 70


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