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)

To investigate the possible role of islet amyloid polypeptide (IAPP) in the development of type 2 diabetes mellitus, we examined the IAPP content and secretion in pancreatic islets isolated from ventromedial hypothalamic (VMH)-lesioned rats and genetically obese Zucker rats, using a specific radioimmunoassay for IAPP. Obesity and hyperinsulinemia were observed in rats 21 days after VMH lesioning. IAPP content was increased in the islets of VMH-lesioned rats compared with findings in the sham-operated controls (100.9 +/- 6.6 vs 72.8 +/- 3.85 fmol/islet; P less than 0.01). Isolated islets of VMH-lesioned rats secreted larger amounts of IAPP in the presence of 2.8 and 16.7 mM glucose (2.99 +/- 0.98 and 11.2 +/- 0.29 fmol islet-1 3 h-1) than was noted in sham-operated rats (ND and 6.65 +/- 0.78 fmol islet-1 3 h-1). In the obese Zucker rats, aged 14 weeks, IAPP concentrations in the islets were elevated compared with lean rats (133.3 +/- 10.6 vs 84.4 +/- 8.5 fmol/islet; P less than 0.01). The isolated islets secreted larger amounts of IAPP in response to 2.8 and 16.7 mM glucose (2.83 +/- 0.88 and 15.81 +/- 1.35 fmol islet-1 3 h-1) than did those from lean control rats (0.36 +/- 0.19 and 12.49 +/- 1.20 fmol islet-1 3 h-1). These results strongly suggest that overproduction and hypersecretion of IAPP occur in animals with obesity and hyperinsulinemia.
Diabetes Res Clin Pract 1992 Jan
PMID:Hypersecretion of IAPP from the islets of VMH-lesioned rats and obese Zucker rats. 154 Dec 31

Twenty pancreata of non-diabetic patients and 17 pancreata of diabetic patients, including two patients with insulin-dependent diabetes mellitus, were immunohistochemically studied using antiserum against human islet amyloid polypeptide (IAPP). The islet beta cells in non-diabetic patients were immunoreactive for both IAPP and insulin. Amyloid deposition immunoreactive for IAPP was detected in six of 20 pancreata of non-diabetic patients. The plasma glucose level of three of these six patients was elevated to more than 200 mg/dl, and that of the other three ranged from 143 to 162 mg/dl; all six were receiving intravenous hyper-alimentation and had no history of diabetes prior to treatment. Amyloid deposition was present in all patients with non-insulin-dependent diabetes mellitus (NIDDM). The deposition was absent in the pancreata of two secondary diabetic patients, one of whom had received steroid hormone for bronchial asthma and the other of whom had liver cirrhosis with hepatocellular carcinoma; deposition was also absent in the pancreas of a patient with impaired glucose tolerance diagnosed on a 75-g oral glucose load. Heterogeneous expression of immunoreactivities of beta cells for insulin and for IAPP was present, suggesting independently regulated production and secretion of the peptides. Immunoreactivity of beta cells was more sensitively decreased for IAPP than for insulin in the islets of NIDDM patients. The decreased immunoreactivity for IAPP suggested an initial stage of disturbed beta-cell function, even if the immunoreactivity for insulin was apparently intact or the amyloid deposition in the islets was insignificant. The degree of amyloid deposition immunoreactivity for IAPP did not necessarily reflect the severity of diabetes mellitus. Amyloid deposits were seen at the narrow spaces beneath the insular capsule of connective tissues and the perivascular region or, in some cases, occupying the whole of the islet. The diabetogenic role of IAPP is unclear, but the deposition might be an accelerating factor which disturbs beta-cell function.
Diabetes Res Clin Pract 1992 Jan
PMID:Islet amyloid polypeptide (IAPP) and pancreatic islet amyloid deposition in diabetic and non-diabetic patients. 154 Dec 32

Using reverse-phase high performance liquid chromatography combined with radioimmunoassays for human and rat/mouse islet amyloid polypeptide (IAPP), we identified molecular forms of IAPPs in pancreata of four mammals including species in which islet amyloid deposition occurs (human and cat) and those in which amyloid deposition does not occur (rat and mouse). In human pancreas, IAPP (1-37) was the major molecular form, and IAPP (17-37), IAPP (24-37) and four IAPP-immunoreactive peptides were detected as minor components. In rat, mouse and cat pancreata, IAPP (1-37) and IAPP (19-37) were identified with the latter being the major molecular form. Major processing takes place at a single arginine residue at position 18 of rat/mouse and cat IAPPs, but not at the histidine at position 18 of human IAPP, indicating that arginine could yield different processing of IAPP between the 3 species and human. Different processing of IAPP by species suggests that processing of IAPP in pancreas is not responsible for islet amyloid formation. Identification of molecular forms of IAPP is helpful in elucidating the physiological function of the IAPP molecule and in determining the type of system regulating biosynthesis and catabolism of the peptide.
Diabetes Res Clin Pract 1992 Jan
PMID:Molecular forms of islet amyloid polypeptide (IAPP/amylin) in four mammals. 154 Dec 33

Islet amyloid polypeptide (IAPP) is a major constituent of pancreatic amyloid deposits in many patients with non-insulin-dependent diabetes mellitus (NIDDM). We analyzed the IAPP gene in a Japanese diabetic with marked islet amyloid deposition. Pancreatic specimens were obtained from an 87-year-old NIDDM patient who had had diabetes for 37 years. All islets (100/100) in his pancreas had IAPP-positive amyloid deposition, and 70% of the area of the islet was replaced by amyloid. We amplified the coding regions as well as the upstream region of the IAPP gene by polymerase chain reaction (PCR). The products of PCR were sequenced, and the sequences of the coding regions were identical to the Caucasian ones. However, the nucleotides of two positions of 5'-upstream and one position of intron 2 were different from the Caucasian data: the upstream region of the IAPP gene in the patient had cytosine substituted for thymine at -259, and had two alleles including cytosine and adenine at -229, respectively. The nucleotide of position 539, that is guanine, was deleted. A possible difference in the IAPP promoting region between the Japanese and Caucasian population was suggested.
Diabetes Res Clin Pract 1992 Jan
PMID:Islet amyloid polypeptide (IAPP) gene analysis in a Japanese diabetic with marked islet amyloid deposition. 154 Dec 34

Effects of rat islet amyloid polypeptide (IAPP) on insulin biosynthesis and secretion were examined in isolated rat islets and mouse beta TC3 cells. Culture of islets or mouse beta TC3 cells for 24 h in the presence of 10(-6) M IAPP and 5.5 mM glucose had no effect on insulin mRNA levels. The rates of proinsulin biosynthesis were not altered in islets incubated in 10(-4)-10(-9) M IAPP. In beta TC3 cells, proinsulin biosynthesis was stimulated by glucose, though no effects of IAPP were shown. Addition of 10(-5) M IAPP to islets incubated in 11 mM glucose decreased the fractional insulin secretion rates; however, the secretion of insulin from beta TC3 cells was not affected by 10(-5) M IAPP. On the other hand, mouse beta TC3 cells expressed the elevated level of IAPP mRNA. Metabolic labeling of beta TC3 cells revealed the synthesis of both proIAPP and mature IAPP. In pulse chase experiments, proIAPP was processed to IAPP in a manner similar to proinsulin. These data indicate that IAPP is a possible polypeptide hormone synthesized in pancreatic beta cells though it is unlikely that IAPP is a physiologically relevant modulator of insulin biosynthesis or secretion.
Diabetes Res Clin Pract 1992 Jan
PMID:Effects of islet amyloid polypeptide (IAPP) on insulin biosynthesis or secretion in rat islets and mouse beta TC3 cells. Biosynthesis of IAPP in mouse beta TC3 cells. 154 Dec 35

It has been reported that islet amyloid polypeptide (IAPP) has insulin antagonistic effects in vivo and in vitro. To determine whether IAPP affects glucose metabolism in skeletal muscle, we performed in situ rat hindlimb perfusion which is a near-physiological system. Forty min after the beginning of insulin infusion at 1000 microU/ml, the synthesized rat amide form of IAPP was infused at 1 nM or 10 nM for 50 min and glucose concentration in the effluent was measured to calculate glucose uptake (GU). The GU did not change during the 1 nM IAPP infusion, but significantly decreased during 10 nM IAPP infusion (554 +/- 24 to 445 +/- 29 nmol/g/min, P less than 0.01). Rat calcitonin gene-related peptide (CGRP), which has sequence homology with IAPP and has been reported to inhibit insulin action, was also administered. Similar to the effect of IAPP, the GU did not change during 1 nM CGRP infusion but significantly decreased during 10 nM CGRP infusion (507 +/- 7 to 323 +/- 15 nmol/g/min, P less than 0.01). In the experiments without insulin infusion, the GU was not changed even by 10 nM IAPP infusion. Therefore, IAPP directly reduced only the insulin-mediated GU in the skeletal muscle, and this effect of IAPP occurred at the same dose as that of CGRP. These data suggest that both IAPP and CGRP may cause insulin resistance in skeletal muscle not through a CGRP receptor but a yet unknown receptor, which has similar binding affinity for both IAPP and CGRP.
Diabetes Res Clin Pract 1992 Jan
PMID:Islet amyloid polypeptide (IAPP/amylin) causes insulin resistance in perfused rat hindlimb muscle. 154 Dec 36

In this study, we compared the effects of islet amyloid polypeptide (IAPP) and calcitonin gene-related peptide (CGRP) on glucose metabolism both in vivo and in vitro in the rat. Intravenous injection of rat CGRP caused a significant increase in plasma glucose concentration with a simultaneous increase in plasma insulin levels, whereas neither IAPP-NH2 nor IAPP-COOH had any effect. Moreover, intravenous infusion of CGRP decreased tolerance to intragastric administration of glucose (O-GTT) without altering plasma insulin levels, but again IAPPs had no effect. On the other hand, 125I-[Tyr0]rat CGRP specifically bound to the liver plasma membrane, and not only CGRP but also IAPP-NH2 dose-dependently displaced the specific binding of 125I-[Tyr0] CGRP, whereas IAPP-COOH had no effect. Conversely, CGRP as well as IAPP-NH2 but not IAPP-COOH evoked dose-dependent activation of adenylate cyclase in the membranes, and these effects were significantly inhibited by a CGRP receptor antagonist, human CGRP-I(8-37). However, neither CGRP nor IAPP-NH2 had any effect on glucose production in rat isolated hepatocytes. These results suggest that (1) IAPP-NH2 but not IAPP-COOH induces adenylate cyclase activation via CGRP receptors on rat liver plasma membranes, and (2) CGRP might not involve its action on the liver in the changes of glucose metabolism.
Diabetes Res Clin Pract 1992 Jan
PMID:Effects of islet amyloid polypeptide (amylin) and calcitonin gene-related peptide (CGRP) on glucose metabolism in the rat. 154 Dec 37

In order to examine the effect of islet amyloid polypeptide (IAPP/amylin), a product of the pancreatic beta cell and a major component of islet amyloid deposits, on exocrine pancreatic function, we studied the effect of rat IAPP amide (IAPP-NH2) on 2-deoxy-D-glucose (2-DG) uptake in isolated mouse pancreatic acini. Mouse pancreatic acini were preincubated for 80 min with various concentrations of IAPP-NH2 (1 nM-1 microM) and [3H]2-DG uptake for 20 min was measured. The full effect of IAPP-NH2 on this function was not immediate but increased linearly with time for up to 80 min of incubation. IAPP-NH2 caused a dose-dependent stimulation of 2-DG uptake by mouse acini; a detectable effect at 10 nM and a maximal effect at 1 microM. In the presence of 1 microM IAPP-NH2, 2-DG uptake increased by 69 +/- 8% above basal (mean +/- SD, n = 6). The results indicate that IAPP-NH2 stimulates glucose uptake in mouse pancreatic acini, and raise the possibility that IAPP-NH2 plays some physiological role in the insuloacinar axis in mouse pancreas.
Diabetes Res Clin Pract 1992 Jan
PMID:Effect of islet amyloid polypeptide (IAPP/amylin) on 2-deoxyglucose uptake in mouse pancreatic acini. 154 Dec 38

The effects of glucose and glucagon on the release of amylin from the isolated perfused rat pancreas were studied. Amylin is a 37-amino acid peptide isolated from pancreatic islet amyloid of patients with non-insulin-dependent diabetes mellitus (NIDDM). Glucose dose-dependently stimulated a biphasic release of amylin from the pancreas in parallel with that of insulin. However, the release of amylin induced by high concentrations of glucose was partially dissociated from that of insulin. The amylin-insulin molar ratios induced by 22.2 mM and 33.3 mM glucose (1.11 +/- 0.05%, 1.05 +/- 0.04%, respectively) were significantly higher than that induced by 16.7 mM glucose (0.90 +/- 0.04%, P less than 0.01 vs 22.2 mM glucose, P less than 0.05 vs 33.3 mM glucose). In the presence of 5.6 mM glucose, glucagon also stimulated the release of amylin from the perfused pancreas in parallel with that of insulin. These findings suggest that amylin may be a secretory protein from the pancreas and that the concomitant secretion of amylin and insulin might contribute to glucose homeostasis.
Diabetes Res Clin Pract 1992 Jan
PMID:Release of amylin from perfused rat pancreas in response to glucose and glucagon. 154 Dec 39

Islet amyloid polypeptide (IAPP/Amylin) is a novel peptide which was extracted from islet amyloid deposits in patients with non-insulin-dependent diabetes mellitus (NIDDM). However, its pattern of secretions and plasma concentrations under various conditions has not yet been made clear enough. In this study, we examined IAPP secretion from islet beta-cells in vitro using cultured islet cells of neonatal rat pancreas and plasma IAPP responses under various conditions in vivo in normal control subjects and patients with glucose intolerance. Our data revealed that (1) IAPP is co-secreted with insulin from islet cells of the rat pancreas by glucose and non-glucose stimuli; (2) fasting plasma IAPP levels in normal control subjects are 24.9 +/- 2.0 pg/ml and the molar ratio of IAPP/insulin is approximately 1/7; (3) fasting IAPP levels are high in obese patients and low in insulin-dependent diabetic patients, and the molar ratio of IAPP/C-peptide in NIDDM patients is lower than that in normal control subjects, suggesting the basal hyposecretion of IAPP relative to insulin in NIDDM; and (4) the obese patients who had a hyperresponsiveness of insulin relative to C-peptide had the hyperresponsiveness of IAPP relative to C-peptide during an oral glucose load, suggesting that IAPP may have some physiological effect in glucose metabolism.
Diabetes Res Clin Pract 1992 Jan
PMID:Islet amyloid polypeptide (IAPP) secretion from islet cells and its plasma concentration in patients with non-insulin-dependent diabetes mellitus. 154 Dec 40


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