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

Pancreatic islets from healthy (control) and neonatally streptozocin-induced diabetic (STZ-D) rats, a model for non-insulin-dependent diabetes mellitus, were incubated with 3H2O and 5.5 or 16.7 mM glucose. At 5.5 mM glucose, no detectable [3H]glucose was formed. At 16.7 mM, 2.2 patom.islet-1.h-1 of 3H was incorporated into glucose by the control islets and 5.4 patom.islet-1.h-1 by STZ-D islets. About 75% of the 3H was bound to carbon-2 of the glucose. Glucose utilization was 35.3 pmol.islet-1.h-1 by the control and 19.0 pmol.islet-1.h-1 by the STZ-D islets. Therefore, 4.5% of the glucose-6-phosphate formed by the control islets and 15.7% by the STZ-D islets was dephosphorylated. This presumably occurred in the beta-cells of the islets catalyzed by glucose-6-phosphatase. An increased glucose cycling, i.e., glucose----glucose-6-phosphate----glucose, in islets of STZ-D rats may contribute to the decreased insulin secretion found in these animals.
Diabetes 1990 Apr
PMID:Glucose cycling in islets from healthy and diabetic rats. 218 Jul 57

Reliable high-recovery human islet storage would facilitate tissue matching, organ sharing, and immune manipulation of donor islets and prospective diabetic recipients. Collagenase-isolated, Ficoll-purified pancreatic islets (median 21,000, 15% of total islet yield) from eight cadaver pancreases were cultured in vitro for 24 h, equilibrated in three steps with dimethyl sulfoxide (DMSO) to a 2-M concentration, supercooled, nucleated, and cooled at 0.25 degree C/min to -40 degrees C before storage at -196 degrees C for 44.25 +/- 8.75 days. Rewarming at 200 degrees C/min and removal of DMSO with 0.75 M sucrose preceded 48 h of culture and retesting. Recovery postthaw by microscope count on duplicate aliquots was 94.2 +/- 3.5% of prefreeze counts and by triplicate assay of extractable insulin was 90.0 +/- 22.3% on day 0 and 74.1 +/- 12.6% after a 48-h culture. Nonfrozen islets increased basal insulin secretion 7.7 +/- 2.8 times after stimulation with 300 mg/dl glucose in perifusion, whereas islets frozen-thawed and cultured 48 h increased 6.2 +/- 0.8 times (NS). Peak stimulated insulin release was 0.92 +/- 0.14 microU.islet-1.min-1 before storage and 0.73 +/- 0.14 microU.islet-1.min-1 (79% of control, NS) after freeze-thaw and a 48-h culture. Total insulin secretion (area under curve) was 66% of prefreeze values at 48 h. Immunocytochemical stains revealed preservation of islet morphology postthaw. Electron microscopy showed intact cellular and nuclear membranes and intracellular organelles. Frozen-thawed islets harvested 14 days after renal subcapsular xenografting in nude mice were revascularized and well granulated. Cryopreservation can achieve prolonged storage of large numbers of human islets with high recovery numerically and functionally, making this a feasible approach for future trials of human islet transplantation.
Diabetes 1989 Mar
PMID:Long-term cryogenic storage of purified adult human islets of Langerhans. 249 64

The addition of 3-aminobenzamide (a potent inhibitor of poly(ADP-ribose)synthetase) into the incubation medium, prevents streptozotocin-induced inhibition of glucose-stimulated insulin release from isolated islets [control 142 +/- 14 microU X islet-1 X h-1; streptozotocin (0.5 mg/ml) 31 +/- 8; 3-aminobenzamide (1.0 mg/ml) 96 +/- 11; streptozotocin plus 3-aminobenzamide 122 +/- 19]. In vivo, intraperitoneal 3-aminobenzamide 300 mg/kg body weight prevents the appearance of overt diabetes in streptozotocin-treated rats. These protective effects of 3-aminobenzamide are dose-dependent and are similar to those exerted by nicotinamide. Taking into account that poly ADP-ribosylation is involved in the repair of damaged DNA, the protection exerted by 3-aminobenzamide against the diabetogenic effect of streptozotocin strongly supports the view that this acute effect may be a major consequence of the activation of DNA repair mechanisms in islet cells.
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PMID:Protective effect of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase, against streptozotocin-induced diabetes. 293 87

Fetal (20-21 day gestation) and neonatal (less than 5-day-old) rat islets were isolated from the glucagon-rich (dorsal) and glucagon-poor (ventral) pancreatic regions. After 1 or 2 wk in culture, groups of islets from each region were transferred to culture dishes containing Krebs-Ringer bicarbonate buffer with low (2.4 mM) and high (16.7 mM) glucose plus aminophylline. After 2 wk in culture, insulin released into medium was higher than after 1 wk, and more so if the islets originated from dorsal tissue (P less than .01). Glucagon release in response to alanine (10 mM) stimulation was also significantly higher in dorsal than in ventral islets (6.38 +/- 1.98 vs. 1.49 +/- 0.89 pg X islet-1 X h-1, respectively; P less than .02). Coincident with higher insulin and glucagon release, islet yield was greater in tissue from the dorsal neonatal pancreas than from that obtained in the fetal and neonatal ventral pancreas [range: dorsal, 131-180 (median, 153), vs. ventral, 53-127 (median, 84), islets obtained on day 5 of culture]. Neonatal islets of dorsal origin were transplanted intrasplenically (500-3000 islets) to streptozocin-induced diabetic inbred Lewis rats. Only rats receiving greater than 2500 islets were cured by transplantation. These experiments show that dorsal fetal islets secrete more insulin than do ventral islets and that islet yield is higher when islets are isolated from dorsal rather than from ventral perinatal pancreatic tissue. Despite their in vitro behavior, more neonatal dorsal islets are required to cure experimental diabetes than are reported with adult islets.
Diabetes 1986 Nov
PMID:Hormone release, islet yield, and transplantation of fetal and neonatal rat dorsal and ventral pancreatic islets. 309 1

The islet-1 (Isl-1) gene encodes a protein that binds to the enhancer region of the insulin gene. Isl-1 is a member of the LIM/homeodomain family of transcription factors. Because insulin deficiency, either relative or absolute, is a cardinal feature of non-insulin-dependent diabetes mellitus (NIDDM), this study addressed the question of whether mutations in genes that regulate insulin production could be involved. Rat Isl-1 was the first insulin enhancer binding protein to be isolated, and, in this study, the rat gene was used to isolate a partial human islet Isl-1 cDNA and subsequently to isolate genomic clones. A simple sequence repeat was found in the Isl-1 gene, and polymerase chain reaction amplification of this region of genomic DNA revealed 12 alleles in St. Louis African-Americans (het = 0.87), 14 alleles in black Nigerians (het = 0.89), 8 alleles in Japanese (het = 0.69), and 8 alleles in Caucasians (het = 0.81). Genetic linkage analysis uniquely placed Isl-1 on chromosome 5q (D5S395[12.8 cM]Isl-1 [11.6 cM]D5S407). The simple sequence repeat polymorphism at the Isl-1 locus was used to evaluate mutations in this gene as a possible contributor to the pathogenesis of NIDDM. Allelic frequencies did not differ between patients with NIDDM (n = 165) and nondiabetic control subjects (n = 163) in two black populations (St. Louis African-Americans and Nigerians). Linkage analyses in 15 nonglucokinase maturity-onset diabetes of the young pedigrees indicated that linkage could be rejected (LOD score < -3.0) over a distance of 15 cM.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1994 Jul
PMID:Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat polymorphism [corrected]. 791 9

A decreased acute insulin response to glucose in islet cell antibody positive humans predicts diabetes. Because the dominant mechanism leading to decreased in vivo acute insulin response to glucose remains unclear, perifused islets were examined before and after diabetes onset in BB rats to assess the role of glucose sensitivity on insulin secretion in individual islets. Islets from normal WF rats, diabetes-prone rats without inflamed islets, diabetes-prone rats with inflamed islets, and diabetic rats were studied at 2.0, 8.3, and 16.7 mM glucose. Immunoreactive insulin from WF islets at 16.7 mM glucose was 0.15 +/- 0.02 ng.0-7 min-1 x islet-1 for the first phase and 1.00 +/- 0.05 ng.7-20 min-1 x islet-1 for the second phase of biphasic secretion, compared with basal secretion of 0.10 +/- 0.03 ng.20 min-1 x islet-1 at 2 mM glucose. Diabetes-prone noninflamed islets showed a 0.20 +/- 0.03 ng first-phase secretion, a 1.32 +/- 0.13 ng second-phase secretion after 16.7 mM glucose, and 0.093 +/- 0.02 ng.20 min-1 x islet-1 at 2 mM glucose, indicating no intrinsic BB rat strain secretion abnormality. Diabetes-prone inflamed islets had secretions of 0.35 +/- 0.02 ng during the first phase (P < 0.05 vs. WF) and 1.78 +/- 0.29 ng during the second phase (P < 0.05 vs. WF) after 16.7 mM glucose, with 0.24 +/- 0.08 ng.20 min-1 x islet-1 at 2 mM glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1993 Sep
PMID:Pancreatic islet function in nondiabetic and diabetic BB rats. 834 42

Pancreatic islets were cultured for 24 h in medium containing either low (1.4), normal (5.5), or high (16.7 mM) glucose, and then insulin secretion was measured at the end of 1 h incubation at 37 degrees C. Insulin release in the absence of glucose was 64 +/- 20, 152 +/- 11, and 284 +/- 30 pg.islet-1.h-1 (mean +/- SE, n = 6, G1.4 and G16.7 vs. G.5.5, P < 0.05) and the response to 22 mM glucose stimulation was 640 +/- 136, 2460 +/- 276, and 1890 +/- 172 pg.islet-1.h-1, respectively (n = 6, G1.4 vs. G5.5, P < 0.01, G16.7 vs. G5.5, P = 0.065). The 50% maximal response of insulin secretion (increment over baseline) was reached at an average glucose concentration of 9.9 +/- 0.7 mM in islets preexposed to G5.5, and at glucose 13.3 +/- 0.9 and 4.8 +/- 0.4 mM (P < 0.05 in respect to G5.5) in islets preexposed to G1.4 and G16.7, respectively. To investigate the molecular mechanism responsible for this altered glucose sensitivity, we measured, in parallel experiments, the kinetic characteristics of glucose transport, glucokinase, and glucose utilization. Glucose transport was measured by evaluating 3-O-methylglucose uptake. The apparent Km of the low-affinity transporter (GLUT2) was 16.6 +/- 2.4 mM in isolated pancreatic cells cultured at 5.5 mM glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1993 Jan
PMID:Glucose modulates glucose transporter affinity, glucokinase activity, and secretory response in rat pancreatic beta-cells. 842 Aug 17

IAPP, or amylin, is a 37-amino acid peptide that is co-secreted with insulin from the pancreatic beta-cells. We have determined the effects of IAPP and the antagonist 8-37 fragment of IAPP on the secretion of insulin from isolated rat islets studied in a perifusion system. Insulin secretion was stimulated by 8 mM glucose and 0.2 microM carbachol. IAPP at 10(-7) M reduced insulin release by 32% from 7.1 (95% Cl 5.8-8.6) to 4.8 (3.0-7.5) fmol.min-1 x islet-1 (P = 0.046, n = 7). IAPP at 1.5 x 10(-6) M reduced insulin release by 62% from 6.5 (3.4-12.3) to 2.5 (1.4-4.4) fmol.min-1 x islet-1 (P = 0.001, n = 6). IAPP at 10(-5) M decreased insulin release by 70% (P < 0.001, n = 6). When IAPP (8-37) at 10(-5) M was added to IAPP at 1.5 x 10(-6) M, there was only a 22% reduction of insulin release (P = 0.06, n = 6) compared with control chambers with no peptide added. This reduction was less (P = 0.002) than observed with IAPP (1.5 x 10(-6) M) alone. IAPP (8-37) at 4 x 10(-5) M in the absence of exogenously added IAPP increased insulin secretion by 48% (P = 0.01, n = 6), but IAPP (8-37) at 10(-5) M did not alter insulin secretion. These findings demonstrate that IAPP decreases insulin secretion from islet beta-cells, an effect that can be antagonized by the 8-37 fragment of IAPP.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1993 Feb
PMID:Influence of islet amyloid polypeptide and the 8-37 fragment of islet amyloid polypeptide on insulin release from perifused rat islets. 842 69

Immunoglobulin (Ig) fractions from the plasma of a group of newly diagnosed insulin-dependent diabetes mellitus (type 1) patients and set of control subjects were assessed for their effects on isolated mouse islet function. It was found that Igs from type 1 patients caused a significant inhibitory effect on insulin secretion when incubated with mouse islets as compared with controls (25.6 +/- 2.9 pg islet-1 h-1 vs 44.7 +/- 7.7 pg islet-1 h-1, P < 0.05). The plasma samples from which the Igs were obtained were then tested for the presence of antibodies to the mouse islet cell surface (ICSA). Four of the nine patients were positive for ICSA, and plasma samples from eight control subjects were all negative. ICSA-positive samples appeared to have the greatest inhibitory effect on insulin secretion when compared with their respective controls (53.3 +/- 7.0 pg insulin islet -1 min-1 vs 30.9 +/- 3.7 pg insulin islet -1 min-1, (P < 0.05). In contrast, it was also found that ICSA-positive Ig fractions had no significant effect on glucose oxidation when co-incubated with mouse islets as compared with the controls (11.3 +/- 2.3 pmol islet-1 h-1 vs 11.2 +/- 2.9 pmol islet-1 h-1). These studies suggest that Igs from newly diagnosed type 1 patients containing ICSA may impair insulin secretion from isolated mouse islets by mechanisms which do not involve the inhibition of B-cell glucose metabolism.
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PMID:The effects of islet cell surface antibodies on the metabolic function of mouse islet B cells in vitro. 859 Jul 83


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