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)

Ghrelin is a gut-brain peptide that has somatotropic, food intake increasing and adipogenic effects. Ghrelin is involved in modulating insulin and glucose metabolism in rodents according to recent studies. In humans acylated ghrelin reduces insulin sensitivity while unacylated ghrelin has opposite effects. In general, ghrelin seems to have diabetogenic effects. Obese, in particular abdominally obese, subjects have low ghrelin levels and decreased total ghrelin levels have been associated with metabolic syndrome and Type 2 diabetes. Most of the human studies in Type 1 diabetes have reported low ghrelin levels probably as a compensatory mechanism against hyperglycaemia. The data on obestatin in the regulation of energy balance is extremely contradictory. Interestingly, ghrelin receptor antagonists may improve glucose tolerance in rats without inducing weight gain by increasing insulin secretion. Antagonism of ghrelin function to treat diabetes is thus a fascinating idea. This review concentrates on recent findings on the orexigenic peptide ghrelin and its derivatives in metabolic disorders with emphasis put on human studies.
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PMID:Ghrelin and metabolic disorders. 1927 67

Poorly controlled diabetes is associated with hormonal imbalances, including decreased prolactin production partially due to increased lactotroph apoptosis. In addition to its metabolic actions, ghrelin inhibits apoptosis in several cell types. Thus, we analyzed ghrelin's effects on diabetes-induced pituitary cell death and hormonal changes. Six weeks after onset of diabetes in male Wistar rats (streptozotocin 70 mg/kg), minipumps infusing saline or 24 nmol ghrelin/day were implanted (jugular). Rats were killed two weeks later. Ghrelin did not modify body weight or serum glucose, leptin or adiponectin, but increased total ghrelin (P<0.05), IGF-I (P<0.01) and prolactin (P<0.01) levels. Ghrelin decreased cell death, iNOS and active caspase-8 (P<0.05) and increased prolactin (P<0.05), Bcl-2 (P<0.01) and Hsp70 (P<0.05) content in the pituitary. In conclusion, ghrelin prevents diabetes-induced death of lactotrophs, decreasing caspase-8 activation and iNOS content and increasing anti-apoptotic pathways such as pituitary Bcl-2 and Hsp70 and serum IGF-I concentrations.
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PMID:Ghrelin treatment protects lactotrophs from apoptosis in the pituitary of diabetic rats. 1954 Mar 4

1. Ghrelin is a multifunctional peptide hormone that affects various processes, including growth hormone and insulin release, appetite regulation, gut motility, metabolism and cancer cell proliferation. Ghrelin is produced in the stomach and in other normal and pathological cell types. It may act as an endocrine or autocrine/paracrine factor. 2. The present article reviews recent findings in the study of ghrelin and its receptor that suggest that the ghrelin gene locus may give rise to a number of functional molecules (peptides and RNA transcripts) in addition to ghrelin. 3. The ghrelin gene encodes a precursor protein, preproghrelin, from which ghrelin and other potentially active peptides are derived by alternative mRNA splicing and/or proteolytic processing. The metabolic role of the peptide obestatin, derived from the preproghrelin C-terminal region, is contentious. However, obestatin has direct effects on cell proliferation. 4. The regulation of ghrelin expression and the mechanisms through which the peptide products arise are unclear. We have recently re-examined the organization of the ghrelin gene and identified several novel exons and transcripts. One transcript, which lacks the ghrelin-coding region of preproghrelin, contains the coding sequence of obestatin. 5. Furthermore, we have identified an overlapping gene on the antisense strand of ghrelin, namely GHRLOS, which generates transcripts that may function as non-coding regulatory RNAs or code for novel, short bioactive peptides. 6. The identification of these novel ghrelin-gene related transcripts and peptides raises critical questions regarding their physiological function and their potential role in obesity, diabetes and cancer.
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PMID:Ghrelin gene-related peptides: multifunctional endocrine / autocrine modulators in health and disease. 1956 30

Ghrelin, a potent gut-brain orexigenic peptide, has a role in stimulation of food intake and long-term regulation of body weight. Metformin and pioglitazone treatment have different effects on body weight. This discrepancy might be related with the effect of these two drugs on plasma ghrelin levels. We investigated the effect of these two drugs on post-prandial acylated and total ghrelin levels in patients with type 2 diabetes. Eleven patients treated with diet, 12 patients treated with 850 mg/day metformin monotherapy and 12 patients treated with 30 mg/day pioglitazone monotherapy for at least 6 months were enrolled in the study. Plasma acylated and total ghrelin levels were investigated at baseline and at the 60 (th), 120 (th), 180 (th), 240 (th) minutes after a mixed meal test. There were no differences between groups in any of baseline metabolic and anthropometric parameters, including acylated and total ghrelin levels. Acylated and total ghrelin concentrations were suppressed similarly after food consumption, and we could not determine any significant difference between the groups at any time interval. A prolonged postprandial suppression of acylated ghrelin concentrations was observed in the pioglitazone treatment group compared with baseline values. In conclusion, total and acylated ghrelin levels after a mixed meal test were similar in type 2 diabetic patients treated with metformin, pioglitazone or diet therapy alone. These results suggest that changes in body weight during metformin and pioglitazone treatment are not associated with plasma ghrelin levels.
Exp Clin Endocrinol Diabetes 2009 Sep
PMID:Total and acylated ghrelin levels in type 2 diabetic patients: similar levels observed after treatment with metformin, pioglitazone or diet therapy. 1962 33

Ghrelin, an acylated peptide produced in the stomach, increases food intake and growth hormone secretion, suppresses inflammation and oxidative stress, and promotes cell survival and proliferation. We investigated the pharmacological potential of ghrelin in the treatment of polyneuropathy in uncontrolled streptozotocin (STZ)-induced diabetes in mice. Ghrelin or desacyl-ghrelin was administered daily for 4 weeks after STZ-induced diabetic polyneuropathy had developed. Ghrelin administration did not alter food intake, body weight gain, blood glucose levels, or plasma insulin levels when compared with mice given saline or desacyl-ghrelin administration. Ghrelin administration ameliorated reductions in motor and sensory nerve conduction velocities in diabetic mice and normalized their temperature sensation and plasma concentrations of 8-isoprostaglandin alpha, an oxidative stress marker. Desacyl-ghrelin failed to have any effect. Ghrelin administration in a mouse model of diabetes ameliorated polyneuropathy. Thus, ghrelin's effects represent a novel therapeutic paradigm for the treatment of this otherwise intractable disorder.
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PMID:Ghrelin reverses experimental diabetic neuropathy in mice. 1973 51

Obese patients with sepsis have higher morbidity and mortality rates than normal weight subjects. One crucial factor is the disease-associated disturbed energy balance. Ghrelin is an orexigenic peptide, mainly produced in the stomach. Leptin is an adipose-tissue derived peptide, circulating as free (fl) and receptor-bound protein (bl) acting antagonistically to ghrelin's effects on food intake. In the present study we tested the weight dependent influence of an intravenous (i.v.) ghrelin injection on leptin levels as well as hepatic protein expression in healthy and endotoxemic rats. Male Lewis rats were randomly divided into four diet-induced obese and four normal weight groups. Application of either ghrelin or NaCl was followed by a bolus injection of LPS or NaCl. Blood was collected at five time points (up to 24 h) to measure fl and bl by radioimmunoassay. Furthermore, hepatic leptin, leptin receptor and ghrelin expression were investigated immunohistochemically. Results revealed a late shift from high elevated fl to significantly enhanced levels of bl in ghrelin treated obese animals. Both fl and bl levels remained unaffected in lean rats. The findings suggest that an increased body weight of the treated animals is associated with altered hormone levels after therapeutic interventions with ghrelin.
Exp Clin Endocrinol Diabetes 2009 Oct
PMID:Ghrelin treatment increases receptor-bound leptin in healthy and endotoxemic obese Lewis rats. 1987 93

Ghrelin is a peptide hormone, which has been isolated from the stomach. It is localized mostly in endocrine cells in the oxyntic mucosa of the stomach. Ghrelin receptors are expressed equally in all parts of the gastrointestinal tract, with a similar level of expression in the mucosal and muscle layers. This peptide hormone has several functions, the most widely known is its growth hormone (GH)-releasing effect. Ghrelin plays an important role in regulating appetite, feeding and energy metabolism. It also plays a role in mediating immune response and inflammatory processes. Ghrelin stimulates gastric motility and emptying as well as motility in the small and large intestine. Ghrelin has been reported to be affected in several gastrointestinal diseases/disorders such as inflammatory bowel disease, coeliac disease, infectious diseases, functional disorders and diabetes gastroenteropathy. This indicates that ghrelin is involved in the pathophysiology of gastrointestinal diseases/disorders. Several studies have shown that ghrelin and its antagonist are a promising tool for treatment of several gastrointestinal diseases/disorders.
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PMID:Ghrelin in gastrointestinal diseases and disorders: a possible role in the pathophysiology and clinical implications (review). 1988 11

Ghrelin and GH secretagogues, including GH-releasing peptide (GHRP)-6, stimulate food intake and adiposity. Because insulin modulates the hypothalamic response to GH secretagogues and acts synergistically with ghrelin on lipogenesis in vitro, we analyzed whether insulin plays a role in the metabolic effects of GHRP-6 in vivo. Streptozotocin-induced diabetic rats received saline, GHRP-6, insulin, or insulin plus GHRP-6 once daily for 8 wk. Rats receiving saline suffered hyperglycemia, hyperphagia, polydipsia, and weight loss. Insulin, but not GHRP-6, improved these parameters (P < 0.001 for all), as well as the diabetes-induced increase in hypothalamic mRNA levels of neuropeptide Y and agouti-related peptide and decrease in proopiomelanocortin. Cocaine amphetamine-related transcript mRNA levels were also reduced in diabetic rats, with GHRP-6 inducing a further decrease (P < 0.03) and insulin an increase. Diabetic rats receiving insulin plus GHRP-6 gained more weight and had increased epididymal fat mass and serum leptin levels compared with all other groups (P < 0.001). In epididymal adipose tissue, diabetic rats injected with saline had smaller adipocytes (P < 0.001), decreased fatty acid synthase (FAS; P < 0.001), and glucose transporter-4 (P < 0.001) and increased hormone sensitive lipase (P < 0.001) and proliferator-activated receptor-gamma mRNA levels (P < 0.01). Insulin normalized these parameters to control values. GHRP-6 treatment increased FAS and glucose transporter-4 gene expression and potentiated insulin's effect on epididymal fat mass, adipocyte size (P < 0.001), FAS (P < 0.001), and glucose transporter-4 (P < 0.05). In conclusion, GHRP-6 and insulin exert an additive effect on weight gain and visceral fat mass accrual in diabetic rats, indicating that some of GHRP-6's metabolic effects depend on the insulin/glucose status.
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PMID:The positive effects of growth hormone-releasing peptide-6 on weight gain and fat mass accrual depend on the insulin/glucose status. 2021 77

The small intestine exhibits numerous hormonal and metabolic functions. These are mediated by enteroendocrine cells that are expressed in addition to enterocytes in the mucosa of the small intestine. The release of cholecystokinin causes the secretion of pancreatic enzymes and a contraction of the gallbladder. Recently, a hormonal regulation of gallbladder filling was confirmed. This is mediated by the hormone FGF15/19 which is secreted by enterocytes of the terminal ileum following induction of its expression by bile acids. In addition, FGF15/19 reduces synthesis of bile acids and fatty acids and inhibits gluconeogenesis. Ghrelin is the only intestinal hormone that increases food intake. Contrary, a number of hormones such as cholecystokinin and glucagon-like peptide are expressed in the small intestine and mediate satiation. Knowledge of the intestinal hormones and their functions is important for the full understanding of metabolic control and provides targets for innovative therapy of several diseases such as diabetes type 2, non-alcoholic steatohepatitis and obesity.
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PMID:[Hormonal and metabolic functions of the small intestine]. 2038 79

Ghrelin is an orexigenic peptide hormone secreted into the systemic circulation predominantly by the X/A-like cells in the mucosa of the stomach. In addiction to central effects on food intake and growth hormone release, ghrelin has also important vascular and metabolic actions. Our laboratory has shown that administration of exogenous ghrelin acutely improves endothelial function by increasing nitric oxide bioavailability and normalizing the alterate balance between endothelin 1/nitric oxide (ET-1/NO) within the vasculature of individuals with metabolic syndrome. Additionally, in endothelial cell cultures, it has been shown that ghrelin directly stimulates NO production using a signaling pathway that involves GHSR-1a, PI 3-kinase, Akt, and eNOS. Other cardiovascular effects of ghrelin include lowering of peripheral resistance, improvement of contractility and cardiac output. In addition ghrelin plays a significant role in the regulation of glucose homeostasis, lipid profiles and body composition. Importantly, ghrelin has antinflammatory and antiapoptotic effects both in vivo and in vitro. This review focuses on the physiological roles of ghrelin in regulating metabolic and endothelial function and on the potential of ghrelin as the therapeutic target to treat metabolic and cardiovascular disorders.
Curr Diabetes Rev 2010 Jul
PMID:Cardiovascular and metabolic effects of ghrelin. 2045 93


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