Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied 65-year old, obese man suspected of obstructive sleep apnoea. He gave a history of loud snoring and excessive daytime sleepiness. We confirmed sleep apnoea syndrome during limited polysomnography with Polymesam (RDI--45/h, ODI--47/h). Patient had mainly obstructive episodes, however central and mixed apnoeas constituted about 1/3 of all episodes. During hospitalization we observed exacerbation of coronary artery disease and diagnosed diabetes. Patient's coarsened facial features, macroglossia and large hands led us to suspect acromegaly. Brain MR study revealed small pituitary adenoma. Plasma GH and IGF-1 concentrations were increased. Active acromegaly was diagnosed and was proposed a surgical treatment but he refused. Symptoms of sleep apnoea relieved after CPAP treatment. After one year patient's condition remained stable.
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PMID:[Acromegaly and sleep apnoea syndrome--case report]. 1192 64

Maturity-onset diabetes of the young type 3 (MODY3) is characterized by impaired insulin secretion. Heterozygous mutations in the gene encoding hepatocyte nuclear factor (HNF)-1alpha are the cause of MODY3. Transgenic mice overexpressing dominant-negative HNF-1alpha mutant in pancreatic beta-cells and HNF-1alpha knockout mice are animal models of MODY3. These mice exhibit defective glucose-stimulated insulin secretion and have reduced beta-cell mass and beta-cell proliferation rate. Here we examined the effect of HNF-1alpha on beta-cell proliferation by overexpressing a human naturally occurring dominant- negative mutation P291fsinsC in INS-1 cells under the control of doxycycline-induction system. INS-1 cells overexpressing P291fsinsC showed apparent growth impairment. The proliferation rate estimated by [(3)H]thymidine incorporation was significantly reduced in P291fsinsC-expressing INS-1 cells compared with noninduced or wild-type HNF-1alpha-overexpressing INS-1 cells. Growth inhibition occurred at the transition from G1 to S cell cycle phase, with reduced expression of cyclin E and upregulation of p27. cDNA array analysis revealed that the expression levels of IGF-1, a major growth factor for beta-cells, and macrophage migration inhibitory factor (MIF), a cytokine expressed in pancreatic beta-cells, were reduced in P291fsinsC-HNF-1alpha-expressing INS-1 cells. Although MIF seemed to have proliferative function, blockade of MIF action by anti-MIF antibody stimulated INS-1 cell proliferation, excluding its direct role in the growth impairment. However, addition of IGF-1 to P291fsinsC-expressing INS-1 cells rescued the growth inhibition. Our data suggest that HNF-1alpha is critical for modulating pancreatic beta-cell growth by regulating IGF-1 expression. IGF-1 might be a potential therapeutic target for the treatment of MODY3.
Diabetes 2002 Jun
PMID:Hepatocyte nuclear factor-1alpha modulates pancreatic beta-cell growth by regulating the expression of insulin-like growth factor-1 in INS-1 cells. 1203 66

A case of acromegaly, secondary to GHRH secretion by a large bronchial carcinoid is reported. A 61-year-old woman presented with typical symptoms and signs of acromegaly for at least 10 years. She suffered from recurrent pneumonias, but repeated chest X-ray examinations failed to demonstrate the bronchial tumor. The diagnosis was confirmed by elevated GH, IGF-1 and GHRH secretion. We have shown an enlarged pituitary gland without focal lesions together with a cerebral meningioma on MRI and the presence of a bronchial carcinoid tumor. The latter was confirmed by histology carried out after bronchoscopy and tumor excision. We observed partial suppression of GH secretion following short-term oral bromocriptine administration in this patient. Surgical removal of the carcinoid tumor resulted in a complete clinical, hormonal and radiological cure of acromegaly. This case of acromegaly due to ectopic GHRH secretion by bronchial carcinoid differs from others described in the literature by an atypical large tumor size, the suppression of elevated GH secretion by oral bromocriptine and a concomitant meningioma.
Exp Clin Endocrinol Diabetes 2002 Jun
PMID:Acromegaly due to GHRH-secreting large bronchial carcinoid. Complete recovery following tumor surgery. 1205 43

The advent of recombinant technology has revealed attractive therapeutic profile of insulin-like growth factor I (IGF-1) in the treatment of chronic cardiovascular diseases such as diabetes and heart failure. However, the safety and potential adverse effect of IGF-1 have not been well defined. This study was designed to evaluate the impact of short-term IGF-1 administration on myocardial contractile function. Adult rats were given recombinant human IGF-1 (3mg/kg/d, s.c.) for 8 weeks. Mechanical properties were evaluated in left-ventricular papillary muscles using a force-transducer. Myocardial contractile properties analyzed included peak tension development (PTD), time-to-peak tension (TPT), time-to-90% relaxation (RT(90)), and maximal velocity of tension development/decline (+/-VT). Short-term IGF-1 treatment enhanced the plasma IGF-1 level but had no effect on body and organ weights. The myocardium from IGF-1-treated rats exhibited enhanced PTD associated with similar TPT, RT(90), and +/-VT compared to the control group. IGF-1-treated myocardium exhibits an enhanced PTD-Ca(2+) response and a better intracellular Ca(2+) replenishing ability at the low stimulus frequencies. Acute application of IGF-1 (1-500 ng/ml) elicited a comparable concentration-dependent increase in PTD in myocardium from both control and the IGF-1-treated groups. Acute IGF-1 application had no effect on +/-VT, TPT, and RT(90) in either group tested. Pretreatment with the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester blunted the IGF-1-induced positive response in myocardium from both control and IGF-1-treated groups. These results suggest that short-term IGF-1 treatment is unlikely to induce IGF-1 resistance in myocardial contractile function.
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PMID:Short-term administration of insulin-like growth factor I (IGF-1) does not induce myocardial IGF-1 resistance. 1216 97

We investigated the relationship between the changes in vascular responsiveness and growth factor mRNA expressions induced by 1-wk treatment with high-dose insulin in control and established streptozotocin (STZ)-induced diabetes. Aortas from diabetic rats, but not those from insulin-treated diabetic rats, showed impaired endothelium-dependent relaxation in response to ACh (vs. untreated controls). The ACh-induced nitrite plus nitrate (NOx) level showed no significant difference between controls and diabetics. Insulin treatment increased NOx only in diabetics. In diabetics, insulin treatment significantly increased the aortic expressions of endothelial nitric oxide synthase (eNOS) mRNA and VEGF mRNA. The expression of IGF-1 mRNA was unaffected by diabetes or by insulin treatment. In contrast, the mRNA for the aortic IGF-1 receptor was increased in diabetics and further increased in insulin-treated diabetics. In aortic strips from age-matched control rats, IGF-1 caused a concentration-dependent relaxation. This relaxation was significantly stronger in strips from STZ-induced diabetic rats. These results suggest that in STZ-diabetic rats, short-term insulin treatment can ameliorate endothelial dysfunction by inducing overexpression of eNOS and/or VEGF mRNAs possibly via IGF-1 receptors. These receptors were increased in diabetes, perhaps as result of insulin deficiency.
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PMID:Short-term insulin treatment and aortic expressions of IGF-1 receptor and VEGF mRNA in diabetic rats. 1238 52

A diabetic acromegalic man, not cured after surgery and radiosurgery, received lanreotide i.m. with great clinical and biochemical improvement. He required NPH insulin (76 to 84 units/day) to control his diabetes mellitus. Thirty-six hours after changing to LAR-octreotide (20 mg i.m/month) he presented symptomatic hypoglycemia, repeated at 48 and 72 h (50 mg/dL), despite reducing insulin to 26 Units/day. Thereafter, he reduced insulin by 30 to 50% for the first week after each LAR-octreotide injection, and gradually increased it again over the next 3 weeks. This situation persists after every injection 3 years later; this consistent behavior supports a specific effect of LAR-octreotide, and not a by chance phenomenon. No marked changes in circulating GH, IGF-1, immunoreative insulin, C-peptide, testosterone and glucose were observed prior to, and 3, 7, 14, 21, and 28 days after LAR-octreotide; however, there was 28% fall in plasma glucagon after 7 days, which rose thereafter. C-peptide (< 1.8 ng/mL) was indicative of decreased beta-cell function. To our knowledge, this is the first report of such a distinct differential behaviour of blood glucose and insulin requirements with different somatostatin analogs, and is worth recalling when starting an insulin-treated diabetic patient on this treatment. It may be related to a preferential binding of LAR-octreotide to subtype 2 somatostatin receptors in the pancreas, while lanreotide preferentially binds to subtype 5, not expressed in this tissue; this would explain the fall in glucagon, in parallel to the decrease in insulin requirements after LAR-octreotide; however, a contribution of differences in the effect of both somatostatin analogues on postreceptor signalling systems and/or intestinal carbohydrate absorption cannot be entirely ruled out.
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PMID:Decreased insulin requirements after LAR-octreotide but not after lanreotide in an acromegalic patient. 1250 80

Growth hormone (GH) has profound effects on vertebrate growth and cellular differentiation in diverse tissue types. Sexually dimorphic levels of circulating GH vary during development and throughout the lifespan. The synthesis and secretion of GH by the pituitary gland are precisely controlled. Abnormal levels are pathological; hyposecretion in children results in dwarfism while hypersecretion results in acromegaly. This review provides an overview of GH and the GH/insulin-like growth factor (IGF-1) axis and highlights a GH receptor antagonist (i.e. Somavert(R), pegvisomant). This antagonist competes with endogenous GH for the receptor and results in suppression of serum insulin-like growth factor (IGF-1). Pegvisomant is important for the treatment of acromegaly and may have therapeutic implications for certain types of cancer and end organ damage due to diabetes.
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PMID:Growth hormone receptor antagonists. 1251 51

We report a 5 year old girl with postnatal overgrowth (height velocity >97th centile), hyperinsulinaemia, and increased insulin-like growth factor 1 for age, without evidence of bioactive or immunoreactive growth hormone excess or pituitary abnormality. Although her overgrowth may be a result of hyperinsulinism, her serum contains a factor (neither insulin nor IGF-1) which is able to stimulate the proliferation of lymphocyte precursors, and this could also account for the overgrowth. Over the course of two years observation she has developed acanthosis nigricans and diabetes mellitus.
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PMID:Hyperinsulinism and overgrowth without obesity. 1265 61

Glucose can activate the mitogen-activated kinases, Erk-1/2, and the ribosomal-S6 kinase, p70(S6K), in beta-cells, contributing to an increase in mitogenesis. However, the signaling mechanism by which glucose induces Erk-1/2 and p70(S6K) phosphorylation activation is undefined. Increased glucose metabolism increases [Ca(2+)](i) and [cAMP], and it was investigated if these secondary signals were linked to glucose-induced Erk-1/2 and p70(S6K) activation in pancreatic beta-cells. Blocking Ca(2+) influx with verapamil, or inhibiting protein kinase A (PKA) with H89, prevented glucose-induced Erk-1/2 phosphorylation. Increasing cAMP levels by GLP-1 potentiated glucose-induced Erk-1/2 phosphorylation via PKA activation. Elevation of [Ca(2+)](i) by glyburide potentiated Erk-1/2 phosphorylation, which was also inhibited by H89, suggesting increased [Ca(2+)](i) preceded PKA for glucose-induced Erk-1/2 activation. Adenoviral-mediated expression of dominant negative Ras in INS-1 cells decreased IGF-1-induced Erk-1/2 phosphorylation but had no effect on that by glucose. Collectively, our study indicates that a glucose-induced rise in [Ca(2+)](i) leads to cAMP-induced activation of PKA that acts downstream of Ras and upstream of the MAP/Erk kinase, MEK, to mediate Erk-1/2 phosphorylation via phosphorylation activation of Raf-1. In contrast, glucose-induced p70(S6K) activation, in the same beta-cells, was mediated by a distinct signaling pathway independent of Ca(2+)/cAMP, most likely via mTOR-kinase acting as an "ATP-sensor."
Diabetes 2003 Apr
PMID:Differential activation mechanisms of Erk-1/2 and p70(S6K) by glucose in pancreatic beta-cells. 1266 69

The insulin resistance-colon cancer hypothesis, stating that insulin resistance may be associated with the development of colorectal cancer, represents a significant advance in colon cancer, as it emphasizes the potential for this cancer to become a modifiable disease. The fact that the incidence of insulin resistance has been increasing in the United States and much of the rest of the Western world where colon cancer remains the second leading cause of cancer death makes the exploration of the interrelationship of these conditions a subject of high priority. Here, we review the salient features of insulin resistance, defined as impaired biological response to the action of insulin. Recent epidemiological studies, evaluating potential associations between colon cancer risk and diabetes mellitus, dietary intake and metabolic factors, and IGF levels in several clinical settings, provide strong support of the insulin resistance-colon cancer hypothesis (without establishing causality). Mechanistically, insulin resistance has been associated with hyperinsulinemia, increased levels of growth factors including IGF-1, and alterations in NF-kappaB and peroxisome proliferator-activated receptor signaling, which may promote colon cancer through their effects on colonocyte kinetics. It is a reasonable expectation that in the not too distant future, critical interventions to the already mapped molecular sequence of events, which link two apparently disparate entities, combined with lifestyle changes could abrogate the development of colon cancer.
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PMID:Insulin resistance and its contribution to colon carcinogenesis. 1267 Nov 84


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