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)

Recombinant DNA techniques have made it possible to establish the structure of various genes encoding polypeptide hormones. Comparison of nucleotide sequences of the calcitonin (CALC) genes in man has revealed surprising similarities and variations. These findings and the homologies among the sequences in different species offered an opportunity for speculation about relationships between these genes and about their evolutionary origin. The first gene (CALC-I) directing the synthesis of calcitonin (CT) or CT gene-related peptide (CGRP) comprises six exons and gives rise to two mRNAs by an alternative RNA-processing mechanism. The homology between CGRP and CT reflects their common origin. The human genome contains a second gene (CALC-II) that is structurally related to the CALC-I gene. The CALC-II RNA transcripts do not appear to be differentially processed, as only preproCGRP-II mRNA and not preproCT-II is detected. The first and second CT/CGRP genes probably have evolved from a common ancestor gene early in evolution. Meanwhile, a third genomic locus containing nucleotide sequences highly homologous to exons 2 and 3 of both CALC genes was detected and probably generated by duplication of a part of CALC-II. This locus is not likely to encode a CT- or CGRP-related polypeptide hormone. The CALC genes and this last (pseudo) gene are located on the short arm of chromosome 11. Recently, islet- or insulinoma-amyloid polypeptide (IAPP) was isolated as a major constituent of amyloid present in human insulinoma and in pancreatic islet amyloid in noninsulin-dependent diabetes mellitus. IAPP shows 46% amino acid sequence homology with human CGRP-II.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evolutionary pathways of the calcitonin (CALC) genes. 263 35

Blood serum levels of calcitonin, parathyroid hormone, calcium, magnesium and inorganic phosphate have been measured in basal condition and following intravenous administration of calcium in 31 patients with diabetes of type I, in 31 patients with diabetes of type II and in 29 healthy subjects. The level of 25-hydroxy cholecalciferol was measured in all these patients in basal condition only. It was found that the basal calcitonin level was significantly higher in patients with both types of diabetes than in healthy subjects. The administration of calcium caused a significantly higher increase in the blood calcitonin level in patients with type I diabetes than in those with type II diabetes. It was found in addition that in women with type II diabetes blood serum level of parathyroid hormone was significantly higher than that in men suffering from diabetes of the same type, suggesting the participation of some sex-related factor in the pathogenesis of the abnormal parathyroid level in these patients.
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PMID:[Serum levels of calcitonin, parathyroid hormone and 25-hydroxycholecalciferol in patients with diabetes mellitus]. 264 13

Amyloid deposits in the islets of Langerhans of the pancreas are a common finding in non-insulin-dependent diabetes mellitus. The main protein constituent of these deposits is a 37-amino acid peptide known as amylin that resembles calcitonin gene-related peptide, a neuropeptide. We have isolated cDNA clones corresponding to the rat amylin precursor from an islet cDNA library and we show that this peptide is encoded in a 0.9-kilobase mRNA that is translated to yield a 93-amino acid precursor. The amylin peptide is bordered by dibasic residues, suggesting that it is proteolyzed like calcitonin gene-related peptide. The peptide sequences flanking the amylin sequence do not resemble the calcitonin gene-related peptide flanking sequences. RNA hybridization studies show that amylin mRNA is abundant in the islets of Langerhans but is not present in the brain or seven other tissues examined. Dietary changes, such as fasting or fasting and refeeding, have little effect on amylin mRNA expression. This tissue specificity suggests that amylin is involved in specific signaling pathways related to islet function.
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PMID:Rat amylin: cloning and tissue-specific expression in pancreatic islets. 265 37

Islet amyloid polypeptide has 37 amino acids and is a major component of amyloid deposition in pancreatic islets of patients with type 2 diabetes mellitus. To determine whether the peptide is involved in the impaired insulin secretion in this type of diabetes mellitus, we synthesized islet amyloid polypeptide and its fragments and examined its effect on insulin secretion. Islet amyloid polypeptide inhibited the glucose-stimulated insulin secretion from isolated rat pancreatic islets, as calcitonin gene-related peptide did, but the fragments failed to inhibit the secretion. Thus, we propose that amyloid deposition may be an important factor in the impairment of insulin secretion in type 2 diabetes mellitus.
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PMID:Islet amyloid polypeptide inhibits glucose-stimulated insulin secretion from isolated rat pancreatic islets. 265 98

We have cloned and sequenced a human islet amyloid polypeptide (IAPP) cDNA. A secretory 89 amino acid IAPP protein precursor is predicted from which the 37 amino acid IAPP molecule is formed by amino- and carboxyterminal proteolytic processing. The IAPP peptide is 43-46% identical in amino acid sequence to the two members of the calcitonin gene-related peptide (CGRP) family. Evolutionary conserved proteolytic processing sites indicate that similar proteases are involved in the maturation of IAPP and CGRP and that the IAPP amyloid polypeptide is identical to the normal proteolytic product of the IAPP precursor. A synthetic peptide corresponding to a carboxyteminal fragment of human IAPP is shown to spontaneously form amyloid-like fibrils in vitro. Antibodies against this peptide cross-react with IAPP from species that develop amyloid in pancreatic islets in conjunction with age-related diabetes mellitus (human, cat, racoon), but do not cross-react with IAPP from other tested species (mouse, rat, guinea pig, dog). Thus, a species-specific structural motif in the putative amyloidogenic region of IAPP is associated with both amyloid formation and the development of age-related diabetes mellitus. This provides a new molecular clue to the pathogenesis of this disease.
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PMID:Islet amyloid polypeptide (IAPP):cDNA cloning and identification of an amyloidogenic region associated with the species-specific occurrence of age-related diabetes mellitus. 267 May 95

Because a series of reports suggests the existence of altered bone and mineral metabolism in diabetes mellitus, we studied 106 diabetic subjects (42 insulin-dependent (IDD) and 64 noninsulin dependent (NIDD] to determine whether a difference in bone turnover (evaluated by serum osteocalcin (OC] could be found in comparison with normal controls. OC levels in diabetic subjects were lower than the age- and sex-specific predicted values. The reduction was especially evident in male and female NIDD (Z-score: - 1.12 +/- 0.92, t = 8.4, P less than 0.001 and -0.84 +/- 0.86, t = 4.0, P less than 0.01, respectively) and male IDD (Z-score: - 0.90 +/- 0.86, t = 4.5, P less than 0.01). The mean Z-score for female IDD, albeit negative (-0.31 +/- 0.79; t = 1.6; 0.2 greater than P greater than 0.1), was not significantly different from normal. Total serum calcium (Ca) and calcitonin (CT) showed an opposite pattern, being higher in all the diabetic subgroups (with the exception of Ca in female IDD), whereas parathyroid hormone (PTH) was lower than expected in each diabetic subset. By multiple regression analysis, the reduction of OC was related to PTH and CT levels and to the type of treatment. Subjects controlled with diet showed differences of greater magnitude from the expected normal values than those treated with oral hypoglycemic agents or insulin (Z-score: -1.28 +/- 1.05 vs. -0.85 +/- 0.90 and -0.63 +/- 0.97, respectively; P = 0.05). However, the variance explained by these three factors was small, suggesting that other variables (possibly 1 alpha,25(OH)2D) exerted important influences on OC levels.
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PMID:Osteocalcin levels in diabetic subjects. 224 99

To assess the affect of mild diabetes on calcium metabolism in an animal model, we evaluated calcium homeostasis before pregnancy and during gestation and lactation in non-insulindependent (NIDD) diabetic rat mothers and their neonates (NeoDM). Plasma glucose, calcium (Ca), magnesium (Mg), phosphate (Pi), and immunoreactive parathyroid hormone (iPTH) were measured in the NIDD rats and controls before pregnancy, during the first, second, and third gestational week, and during lactation 12, 24, 48 and 72 h postpartum. The same measurements were performed on NeoDM and controls 12, 24, 48, and 72 h after birth. In the mothers, plasma calcitonin was assayed before pregnancy and at 72 h postpartum. Higher plasma glucose values before pregnancy (216 +/- 9 mg/dl vs 126 +/- 4) and during the second (105 +/- 5 vs 73 +/- 6) and third (114 +/- 8 vs 91 +/- 3) gestational week were observed in diabetic mothers when compared to controls. Glucose values decreased during the second and third gestational week in both groups compared to pregestational values. Plasma Ca, Mg, and Pi were similar in both groups during gestation and lactation except for the third gestational week when plasma Mg was lower in the diabetic mothers (P less than 0.05). Plasma iPTH rose to similar values in both groups during pregnancy. During lactation, plasma iPTH levels were higher and plasma calcitonin levels were lower compared to controls (P less than .05, P less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mineral homeostasis in neonates of streptozotocin-induced noninsulin-dependent diabetic rats and in their mothers during pregnancy and lactation. 295 60

Amyloid deposits localized to the islets of Langerhans are typical of non-insulin-dependent human diabetes mellitus and of diabetes mellitus in adult cats. Amyloid deposits also commonly occur in insulin-producing pancreatic tumors. We have purified a major protein--insulinoma or islet amyloid polypeptide (IAPP)--from human and cat islet amyloid and from amyloid of a human insulinoma. IAPP from human insulinoma contained 37 amino acid residues and had a theoretical molecular mass of 3850 Da. The amino acid sequence is unique but has greater than 40% identity with the human calcitonin gene-related peptide. A partial amino acid sequence of cat islet IAPP corresponding to positions 1-27 of human insulinoma IAPP was identical to the human IAPP except for substitutions in three positions. An antiserum raised to a synthetic human insulinoma IAPP-(7-17) undecapeptide showed specific immunohistochemical reactivity with human and cat islet amyloid and with islet B cells. The significance of this pancreatic neuropeptide-like protein is unknown, but it is suggested that it may exert an important endocrine regulatory effect.
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PMID:Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells. 303 56

Insulin resistance occurs in a variety of conditions, including diabetes, obesity and essential hypertension, but its underlying molecular mechanisms are unclear. In type 2 (non-insulin-dependent) diabetes mellitus, it is insulin-resistance in skeletal muscle, the chief site of insulin-mediated glucose disposal in humans, that predominantly accounts for the low rates of glucose clearance from the blood, and hence for impaired glucose tolerance. Human type 2 diabetes is characterized by a decrease in non-oxidative glucose storage (muscle glycogen synthesis), and by the deposition of amyloid in the islets of Langerhans. Amylin is a 37-amino-acid peptide which is a major component of islet amyloid and has structural similarity to human calcitonin gene-related peptide-2 (CGRP-2; ref. 8). CGRP is a neuropeptide which may be involved in motor activity in skeletal muscle. We now report that human pancreatic amylin and rat CGRP-1 are potent inhibitors of both basal and insulin-stimulated rates of glycogen synthesis in stripped rat soleus muscle in vitro. These results may provide a basis for a new understanding of the molecular mechanisms that cause insulin resistance in skeletal muscle.
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PMID:Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro. 305 May 30

Amyloid deposits occurring in the islets of Langerhans in patients with noninsulin-dependent diabetes mellitus and some insulinomas contain a 37-amino acid peptide that is structurally related to calcitonin gene-related peptide. We have identified three cDNA clones encoding islet amyloid polypeptide (IAPP) or diabetes-associated peptide (DAP) by oligonucleotide screening of a lambda gt10 human insulinoma cDNA library. Two of the three cDNAs contained a domain encoding IAPP/DAP but had an intron-like sequence in their 5' region. The other cDNA contained an open reading frame encoding an 89-amino acid precursor having a typical signal peptide followed by a small prohormone-like sequence containing within it the IAPP/DAP peptide bracketed at its NH2 and COOH termini by Lys-Arg and Gly-Lys-Arg, respectively. These data indicate that this amyloid peptide is generated by proteolytic processing similar to that for proinsulin and other islet prohormones and also that the peptide may be carboxyamidated. The isolation of cDNA clones having 5'-unprocessed intron-like sequences suggests that inefficient or alternative splicing of this mRNA occurred in the insulinoma.
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PMID:An islet amyloid peptide is derived from an 89-amino acid precursor by proteolytic processing. 305 5


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