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)

Hypothalamic tissue levels of nine regulatory peptides (bombesin, calcitonin gene-related peptide [CGRP], galanin, neuromedin B, neuropeptide Y [NPY], neurotensin, somatostatin, substance P, and vasoactive intestinal peptide [VIP]) were compared in Aston obese diabetic (ob/ob) and lean (+/?) mice aged 4, 16, and 28 weeks. Neurotensin concentrations were significantly lower in ob/ob mice than in lean mice, with a 20% reduction (P = .03) in the whole hypothalamus at 4 weeks of age, a 24% reduction (P = .009) in the lateral hypothalamus at 16 weeks, and a 50% reduction (P = .0007) in the central hypothalamus at 28 weeks of age. Apart from a 42% increase in vasoactive intestinal peptide concentrations in the central hypothalamus of ob/ob mice at 28 weeks (P = .02), levels of the other eight peptides examined did not differ significantly between obese and lean groups. Neurotensin is known to cause anorexia and increased energy expenditure when injected into the central hypothalamus. Reduced hypothalamic neurotensin concentrations may reflect reduced neurotensinergic activity, which might contribute to hyperphagia and decreased energy expenditure, two major defects that contribute to obesity and diabetes in the ob/ob syndrome.
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PMID:Reduced hypothalamic neurotensin concentrations in the genetically obese diabetic (ob/ob) mouse: possible relationship to obesity. 194 36

In this review, we examine the changes in sexual function that accompany deviations from "normal" physiological states. We propose that the changes one observes in many altered physiological states should not be viewed in isolation. We describe our paradigms for assessing sexual function, and proceed to evaluate how sexual function changes with hormonal deprivation and aging, in rat models for hypertension, in severe hyperprolactinemia, in streptozotocin-induced diabetes, after chronic alcohol intake, after chronic morphine administration, and after exposure to the heavy metal, cadmium. We will provide evidence for the involvement of adrenergic transmitters and two neuropeptides, neuropeptide Y and somatostatin, in the neuroendocrine regulation of sexual behavior. Finally, we compare and contrast the changes observed relative to the changes seen in "normal" aging in rats. The sequence of age-related changes in sexual function is distinct. The first change observed is a decrement in ex copula erectile reflexes. Next are decreases in ejaculatory threshold, followed shortly by increases in initiation and reinitiation of copulation after ejaculation. This is followed by a decrement in the number of males copulating to ejaculation. Finally, there is a failure to initiate the copulatory process. This sequelae is relatively common, being evident after castration, with hyperprolactinemia, and after exposure to cadmium. The data available for sexual function in hypertension is incomplete and modified by the etiology, but a suggestion for this sequelae is seen in SHR. In contrast, sexual dysfunction associated with chronic morphine administration appears to be due to an initial deficit in motivational aspects. Testosterone reverses sexual dysfunction associated with castration, but not with idiopathic sexual inactivity, nor with sexual dysfunction associated with aging, diabetes, or chronic morphine administration. Comparing sexual function in rat models for hypertension, diabetes and chronic ethanol leads to the conclusion that increases in blood pressure, like decreases in testosterone, cannot be the primary causal factor for sexual dysfunction. Age, hormonal history of the subject, and the age at castration influence changes in sexual function. Age-related sexual dysfunction appears to be contributed to by changes in adrenergic-neuropeptidergic, to include sympathetic, systems. Site-specific administration of NPY induces alterations in parameters of copulatory behavior which mimic those seen in aging and the retention of ejaculatory behavior with aging is associated with site-selective attenuation (or reversal) of age-associated changes in NPY content. Yohimbine enhances copulatory activity in castrated and aging rats, and attenuates or reverses the antisexual effects of clonidine, epinephrine and somatostatin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sexual function in altered physiological states: comparison of effects of hypertension, diabetes, hyperprolactinemia, and others to "normal" aging in male rats. 763 May 83

Diabetes is associated with altered autonomic activity, and both the peripheral and central nervous content of NPY is altered in diabetes suggesting that part of the cardiovascular dysfunction of diabetes may be associated with altered responses to NPY. We evaluated the mean arterial pressure (MAP), heart rate (HR) and regional blood flow (BF) in response to NPY in normal and diabetic rats. Male Wistar rats were made diabetic using streptozotocin and maintained without insulin treatment for 28-30 days. Normal and diabetic animals were anesthetized, the femoral artery cannulated, and flow probes placed around the iliac, renal and superior mesenteric arteries. Dose dependent responses to NPY infusion were determined for MAP, HR and BF. Conductance was calculated from BF/MAP. In normal rats NPY increased the MAP in a dose-dependent fashion but did not alter the HR. NPY decreased the BF in the iliac artery in a dose-dependent fashion while the renal BF was decreased only at the highest dose, and the superior mesenteric BF was not affected. The conductances in all vascular beds were decreased dose dependently. NPY in diabetic rats also increased MAP and did not affect HR. In diabetic rats NPY also decreased BF in iliac and renal arteries but contrastingly increased BF in the superior mesenteric artery. Again conductances in all three vascular beds were decreased by NPY. When comparing diabetic response to NPY to normals we noted that the MAP response was less in the diabetic, but the HR and regional BF were not different. The vascular conductances in response to NPY were attenuated in the diabetic vessels especially the iliac and superior mesenteric. We conclude that systemic NPY increases MAP as a result of decreased vascular conductance and this vasopressive effect of NPY is diminished in diabetics.
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PMID:Regional vascular and cardiac responses to systemic neuropeptide-Y in normal and diabetic rats. 928 29

Prevertebral sympathetic ganglia develop markedly enlarged argyrophilic neurites as a function of age, gender and diabetes. Immunolocalization studies demonstrate their preferential labeling with antisera to highly phosphorylated 200 kDa neurofilament (NF-H) epitopes, NPY, peripherin and synapsin I, but not to hypophosphorylated NF-M and NF-H or MAP-2. The immunophenotype of dystrophic neurites in conjunction with the results of histochemical and ultrastructural studies are consistent with the terminal axonal and/or synaptic origin of neuritic dystrophy in the sympathetic ganglia of aged and diabetic human subjects.
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PMID:Axonal cytoskeletal pathology in aged and diabetic human sympathetic autonomic ganglia. 937 10

The rat diabetes susceptibility gene, Lyp or Lymphopenia, has been localized to RNO4. Proximal to Lyp are the genes caspase-2 (Casp2) and pancreatic trypsin 1 (Prss1), while neuropeptide Y (Npy) is the closest distally positioned gene. In human, the three genes are syntenic on HSA7, but they are not on a conserved segment: CASP2 and PRSS1 are localized to 7q35, while NPY is localized to 7p15.1. This raises the question whether the human homologue of Lyp is linked to CASP2/PRSS1 or to NPY. We present a comparative map of the Lyp region in rat and human, assigning the gene to a 1.3-Mb segment between RNY3 and ABP1 at 7q35.
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PMID:Comparative mapping of the human homologue of the rat diabetes susceptibility gene lyp to a 1.3-Mb segment on HSA7. 1077 70

The brain contains a subpopulation of glucosensing neurons that alter their firing rate in response to elevated glucose concentrations. In pancreatic beta-cells, glucokinase (GK), the rate-limiting enzyme in glycolysis, mediates glucose-induced insulin release by regulating intracellular ATP production. A similar role for GK is proposed to underlie neuronal glucosensing. Via in situ hybridization, GK mRNA was localized to hypothalamic areas that are thought to contain relatively large populations of glucosensing neurons (the arcuate, ventromedial, dorsomedial, and paraventricular nuclei and the lateral area). GK also was found in brain areas without known glucosensing neurons (the lateral habenula, the bed nucleus stria terminalis, the inferior olive, the retrochiasmatic and medial preoptic areas, and the thalamic posterior paraventricular, interpeduncular, oculomotor, and anterior olfactory nuclei). Conversely, GK message was not found in the nucleus tractus solitarius, which contains glucosensing neurons, or in ependymal cells lining the third ventricle, where others have described its presence. In the arcuate nucleus, >75% of neuropeptide Y-positive neurons also expressed GK, and most GK+ neurons also expressed KIR6.2 (the pore-forming subunit of the ATP-sensitive K+ channel). The anatomic distribution of GK mRNA was confirmed in micropunch samples of hypothalamus via reverse transcription-polymerase chain reaction (RT-PCR). Nucleotide sequencing of the recovered PCR product indicated identity with nucleotides 1092-1411 (within exon 9 and 10) of hepatic and beta-cell GK. The specific anatomic localization of GK mRNA in hypothalamic areas known to contain glucosensing neurons and the coexpression of KIR6.2 and NPY in GK+ neurons support a role for GK as a primary determinant of glucosensing in neuropeptide neurons that integrate multiple signals relating to peripheral energy metabolism.
Diabetes 2000 May
PMID:Localization of glucokinase gene expression in the rat brain. 1090 75

Although exogenous orexin can induce feeding, reports of increased orexin gene expression after caloric manipulations have been inconsistent. We hypothesized that orexin gene expression is increased only by extreme negative energy balance challenges. We measured hypothalamic orexin and NPY mRNA by in situ hybridization and orexin-A immunoreactivity in rats after food deprivation, streptozotocin-induced diabetes, and combined deprivation and diabetes. Neither food deprivation, nor diabetes, nor the combination affected orexin mRNA levels, although orexin-A immunoreactivity was increased by diabetes. NPY mRNA levels were increased by either treatment. These results suggest that increased orexin gene expression is not a consistent correlate of negative energy balance challenges.
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PMID:The effect of food deprivation and experimental diabetes on orexin and NPY mRNA levels. 1178 7

Ghrelin, an endogenous ligand for the growth hormone (GH) secretagogue receptor, was originally purified from the rat stomach. We have previously reported that central administration of ghrelin increases food intake and body weight. To investigate the role of ghrelin in the hyperphagic response to uncontrolled diabetes, adult male rats were studied 14 days after administration of streptozotocin (STZ) or vehicle. STZ-treated diabetic rats were markedly hyperphagic. This hyperphagia was accompanied by hyperglycemia, hypoinsulinemia, and reduced plasma GH levels. Treatment of diabetic rats with insulin reversed these changes. Plasma ghrelin concentrations in untreated diabetic rats were significantly higher than in control rats and were normalized by insulin treatment. The ghrelin gene expression in the stomach was also higher in STZ diabetic rats than in control rats, but this difference was not significant. In contrast, plasma leptin was markedly reduced in STZ diabetic rats. This reduction in plasma leptin levels was reversed by insulin treatment. In addition, hypothalamic NPY mRNA levels were increased in STZ-treated diabetic rats and were reversed by insulin treatment. Furthermore, the hyperphagia was partially reversed by the administration of a ghrelin-receptor antagonist. Therefore, we conclude that the elevated plasma ghrelin levels, along with decreased plasma leptin levels, could contribute to the diabetic hyperphagia in part by increasing hypothalamic NPY. This is the first report to show the pathophysiological significance of ghrelin in diabetes.
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PMID:Role of ghrelin in streptozotocin-induced diabetic hyperphagia. 1244 21

Obesity is associated with many comorbid conditions including diabetes, hyperlipidemia, and gallstones. However, the interaction among these modalities remains unclear. We recently demonstrated that both leptin-deficient and leptin-resistant obese mice have impaired biliary motility. These obese mice also are diabetic and hyperlipidemic. Therefore, we tested the hypothesis that serum glucose, insulin, cholesterol, and triglyceride levels would correlate with gallbladder contractility. Thirty-four lean control, 10 lean heterozygous leptin-deficient, 18 obese homozygous leptin-deficient, and 12 obese homozygous leptin-resistant mice were fed a nonlithogenic chow diet while nine lean control and nine obese homozygous leptin-deficient mice were fed a high-cholesterol diet for 4 weeks. In vitro gallbladder responses to cholecystokinin (CCK; 10(-8) mol/L), acetylcholine (ACh; 10(-5) mol/L), and neuropeptide Y (NPY; 10(-6) mol/L) were measured. Serum glucose, insulin, cholesterol, and triglyceride levels were measured from pooled serum from an additional 704 animals. Gallbladder responses were greatest for CCK, intermediate for ACh, and least for NPY. Serum glucose, insulin, cholesterol, and triglyceride levels and body weight all correlated similarly, negatively, and significantly (P<0.001) with gallbladder contractility. Hyperglycemia, insulin-resistance, hyperlipidemia, and body weight in obese mice with leptin dysfunction are associated with poor gallbladder contractility, which in turn may contribute to the association between obesity and gallstone formation.
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PMID:Diabetes and hyperlipidemia correlate with gallbladder contractility in leptin-related murine obesity. 1459 58

The rat insulinoma cell line RINm5F, an insulin secreting pancreatic beta cell line, has been used as an attractive model for basic studies of the mechanisms of insulin secretion and, more recently, as a model for the development of alternative methods for the treatment of diabetes. To elucidate the cytological properties and expression patterns of hormones of the gastro-entero-pancreatic system, suspensions of RINm5F cells were investigated by various methods including immunocytochemistry on serial semithin sections, quantitative immunocytochemistry, routine electron microscopy, immuno-electron microscopy, in situ hybridization, and TUNEL technique. At the ultrastructural level, several phenotypes of RIm5F cells were characterized by differences in the number, shape, size, and density of their secretory granules. The most common type contained a mixture of round granules varying in size and electron density. A second type predominantly contained relatively large, moderately dense granules. Moreover, a minority of cells was characterized by the occurrence of polymorphous electron dense granules or the complete absence of any secretory granules. The immunohistochemical data showed that, among the established islet hormones, insulin was present in more than 50% of cells, whereas glucagon and somatostatin occurred only sporadically. Though cells positive for pancreatic polypeptide (PP) were not found, PP-related peptides (NPY and PYY) however could be detected in a minority of cells. The great majority of RINm5F cells were immunoreactive for chromogranin B (CgB), followed by insulin, chromogranin A (CgA), and serotonin (5-HT). In addition to intercellular differences in the density of immunostaining, numerous colocalizations of immunoreactivities were found, suggesting that RINm5F cells represent a mixture of subtypes concerning the individual pattern of hormone expression. The present results reveal a wide range of heterogeneity with respect to the morphology and especially the hormone content between individual RINm5F cells.
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PMID:Cytological and immunocytochemical characterization of the insulin secreting insulinoma cell line RINm5F. 1512 25


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