Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Albright hereditary osteodystrophy (AHO) is a genetic disorder caused by heterozygous inactivating mutations in GNAS, the gene that encodes the alpha-chain of Gs (G alpha s). This syndrome is associated with short stature, obesity, brachydactyly, and subcutaneous ossifications. Patients with GNAS mutations on maternally-inherited alleles are resistant to multiple G-protein-coupled hormones, including parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), luteinizing hormone/follicle-stimulating hormone (LH/FSH), and glucagon. This variant of AHO, termed pseudohypoparathyroidism (PHP) type 1a, is due to tissue-specific paternal imprinting of G alpha s. We investigated whether patients with PHP type 1a exhibited evidence of resistance to growth hormone releasing hormone (GHRH) (1), another hormone requiring G alpha s function. In addition, G alpha s transcripts are imprinted in the pituitary somatotrophs responsible for growth hormone (GH) secretion which could thereby influence GHRH-dependent stimulation of somatotrophs. We therefore hypothesized that patients with PHP type 1a may be GH deficient which could contribute to the obesity and short stature in this condition. We found that GH deficiency is common in PHP type 1a (69%) with a prevalence that is much greater than in the general population (0.03%). We propose that GH status be evaluated in all patients with this condition. Treatment with recombinant GH could lead to improvements in height in children, as well as other physical (eg, obesity, hyperlipidemia, osteoporosis, reduced renal function) and psychological (fatigue and diminished sense of well-being) parameters in GH-deficient PHP type 1a patients of all ages.
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PMID:Short stature, obesity, and growth hormone deficiency in pseudohypoparathyroidism type 1a. 1667 31

Several data suggest that fermentable dietary fiber could play a role in the control of obesity and associated metabolic disorders. The aim of this study was to investigate the putative role of short chain fructo-oligosaccharide (OFS) - a non-digestible oligosaccharide - in mice fed a standard diet and in mice fed two distinct high fat diets inducing metabolic disorders associated to obesity. We confirmed, in mice, several effects previously shown in rats fed a standard diet enriched with OFS, namely an increase in total and empty caecum weight, a significant decrease in epididymal fat mass, and an increase in colonic and portal plasma glucagon-like peptide-1 (GLP-1), a phenomenon positively correlated with a higher colonic proglucagon mRNA level. Curiously, 4-week treatment with OFS added at the same dose induced different effects when added in the two different high fat diets. OFS decreased energy intake, body weight gain, glycemia, and epididymal fat mass only when added together with the high fat-carbohydrate free diet, in which OFS promoted colonic proglucagon expression and insulin secretion. Our results support an association between the increase in proglucagon expression in the proximal colon and OFS effects on glycemia, fat mass development, and/or body weight gain. In conclusion, dietary oligosaccharides would constitute an interesting class of dietary fibers promoting, in certain conditions, endogenous GLP-1 production, with beneficial physiological consequences. This remains to be proven in human studies.
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PMID:Relation between colonic proglucagon expression and metabolic response to oligofructose in high fat diet-fed mice. 1675 2

A 60-year-old woman presented to her primary care physician with fatigue and anemia. Laboratory evaluation revealed a hemoglobin level of 9.8 g/dL and an erythrocyte sedimentation rate (ESR) of 64 mm/hour. She subsequently developed nocturnal episodes of diaphoresis, confusion, and hypothermia. Capillary glucose measurements during the spells revealed hypoglycemia. During two supervised fasts, the patient's plasma glucose levels fell to 35 mg/dL and 32 mg/dL, respectively. Plasma insulin and C-peptide levels were appropriately suppressed, but a low concentration of beta-hydroxy-butyrate and normal increase of plasma glucose concentration after a glucagon injection suggested the presence of an insulin-like substance. Computed tomographic (CT) scan of the abdomen and subsequent positron emission tomographic (PET) scan revealed extensive lymphadenopathy. Biopsy of periaortic lymph nodes revealed Hodgkin's disease of the mixed cellularity type. Following chemotherapy, a complete remission ensued, the spells abated, and hypoglycemia was not induced by a 23-hour fast. We believe that the patient's Hodgkin's disease was producing an insulin-like substance. The observations of others suggest that this substance may be an autoantibody to the insulin receptor.
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PMID:Recurrent hypoglycemia and hypothermia in a patient with Hodgkin's disease. 1719 56

To evaluate the energy condition of cattle with growth retardation, propionate (PTT) and arginine tolerance tests (ATT) were carried out. The insulin/glucagon concentration ratio immediately before PTT or ATT in the cattle with growth retardation was lower than in the control. In the growth-retarded cattle, insulin-AUC(0-120 min) during PTT was lower than in the control, while glucagon-AUC(0-120 min) was the same as in the control. Insulin-AUC(0-120 min) during ATT in the cattle with growth retardation tended to be lower than in the control, whereas glucagon-AUC(0-120 min) was the same. Therefore, insulin-AUC(0-120 min)/glucagon-AUC(0-120 min) in the cattle with growth retardation was lower than in the control during both tolerance tests. The growth-retarded cattle showed lower insulin/glucagon ratio similar to that found in starved and lactating cattle, suggesting a lack of energy.
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PMID:Insulin and glucagon secretory patterns during propionate and arginine tolerance tests in Japanese black cattle with growth retardation. 1728 4

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are the members of the glucagon superfamily and bind to common receptors while PACAP also acts via the PACAP-specific receptor, PAC1. The aim of the present study was to investigate whether intracerebroventricular (i.c.v.) injection of VIP and PACAP acts in a similar or different manner to affect body temperature and energy expenditure in the domestic chick. I.c.v. injection of VIP did not significantly affect rectal temperature, but decreased energy expenditure. On the other hand, i.c.v. injection of PACAP significantly increased both body temperature and energy expenditure. These specific actions of PACAP could be explained by an interaction with the PAC1 receptor, since they were partly, but not entirely, attenuated by PACAP (6-38), a PAC1 receptor antagonist. In addition, it was observed that central administration of both VIP and PACAP induced a reduction in respiratory quotient and increased plasma non-esterified fatty acid concentrations. This suggests that both peptides act centrally to regulate a catabolic response. In summary, brain VIP and PACAP both appear to exert generally catabolic effects on energy metabolism in the chick, but their influence on body temperature and glucose metabolism differs and their central effects do not appear to be mediated by the same receptors.
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PMID:Central administration of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide differentially regulates energy metabolism in chicks. 1729 2

The absence of GLUT4 severely impairs basal glucose uptake in vivo, but does not alter glucose homeostasis or circulating insulin. Glucose uptake in isolated contracting skeletal muscle (MGU) is also impaired by the absence of GLUT4, and onset of muscle fatigue is hastened. Whether the body can compensate and preserve glucose homeostasis during exercise, as it does in the basal state, is unknown. One aim was to test the effectiveness of glucoregulatory compensation for the absence of GLUT4 in vivo. The absence of GLUT4 was also used to further define the role of hexokinase (HK) II, which catalyses glucose phosphorylation after it is transported in the cell. HK II increases MGU during exercise, as well as exercise endurance. In the absence of GLUT4, HK II expression will not affect MGU. A second aim was to test whether, in the absence of GLUT4, HK II retains its ability to increase exercise endurance. Wild-type (WT), GLUT4 null (GLUT4(-/-)), and GLUT4 null overexpressing HK II (GLUT4(-/-)HK(Tg)) mice were studied using a catheterized mouse model that allows blood sampling and isotope infusions during treadmill exercise. The impaired capacity of working muscle to take up glucose in GLUT4(-/-) is partially offset by an exaggerated increase in the glucagon: insulin ratio, increased liver glucose production, hyperglycaemia, and a greater capillary density in order to increase the delivery of glucose to the exercising muscle of GLUT4(-/-). Hearts of GLUT4(-/-) also exhibited a compensatory increase in HK II expression and a paradoxical increase in glucose uptake. Exercise tolerance was reduced in GLUT4(-/-) compared to WT. As expected, MGU in GLUT4(-/-)HK(Tg) was the same as in GLUT4(-/-). However, HK II overexpression retained its ability to increase exercise endurance. In conclusion, unlike the basal state where glucose homeostasis is preserved, hyperglycaemia results during exercise in GLUT4(-/-) due to a robust stimulation of liver glucose release in the face of severe impairments in MGU. Finally, studies in GLUT4(-/-)HK(Tg) show that HK II improves exercise tolerance, independent of its effects on MGU.
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PMID:Glucose kinetics and exercise tolerance in mice lacking the GLUT4 glucose transporter. 1749 42

Gastric emptying is a major determinant of glycemia, gastrointestinal hormone release, and appetite. We determined the effects of different intraduodenal glucose loads on glycemia, insulinemia, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and cholecystokinin (CCK), antropyloroduodenal motility, and energy intake in healthy subjects. Blood glucose, plasma hormone, and antropyloroduodenal motor responses to 120-min intraduodenal infusions of glucose at 1) 1 ("G1"), 2) 2 ("G2"), and 3) 4 ("G4") kcal/min or of 4) saline ("control") were measured in 10 healthy males in double-blind, randomized fashion. Immediately after each infusion, energy intake at a buffet meal was quantified. Blood glucose rose in response to all glucose infusions (P < 0.05 vs. control), with the effect of G4 and G2 being greater than that of G1 (P < 0.05) but with no difference between G2 and G4. The rises in insulin, GLP-1, GIP, and CCK were related to the glucose load (r > 0.82, P < 0.05). All glucose infusions suppressed antral (P < 0.05), but only G4 decreased duodenal, pressure waves (P < 0.01), resulted in a sustained stimulation of basal pyloric pressure (P < 0.01), and decreased energy intake (P < 0.05). In conclusion, variations in duodenal glucose loads have differential effects on blood glucose, plasma insulin, GLP-1, GIP and CCK, antropyloroduodenal motility, and energy intake in healthy subjects. These observations have implications for strategies to minimize postprandial glycemic excursions in type 2 diabetes.
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PMID:Load-dependent effects of duodenal glucose on glycemia, gastrointestinal hormones, antropyloroduodenal motility, and energy intake in healthy men. 1760 58

The metabolic state affects the level of general activity of an organism. Satiety is related to relaxation while hunger is coupled to elevated activity which supports the chance to balance the energy deficiency. The unrestricted food availability in modern industrial nations along with no required locomotor activity are risk factors to develop disorders such as obesity. One of the strategies to find new targets for future treatment of metabolic disorders in men is to gain detailed knowledge of molecular and cellular mechanisms involved in the regulation of metabolic homeostasis in less complex, i.e. invertebrate systems. This review reports recent molecular studies in insects about how hunger signals may be linked to global activation. Adipokinetic peptide hormones (AKHs) are the insect counterpart to the mammalian glucagon. They are released upon lack of energy and mobilize internal fuel reserves. In addition, AKHs stimulate the locomotor activity which involves their activity within the central nervous system. In the cockroach Periplaneta americana various neurons express the AKH receptor. Some of these, the dorsal unpaired median (DUM) neurons belonging to a general arousal system, release the biogenic amine octopamine, the insect counterpart to mammalian adrenergic hormones. The two Periplaneta AKHs activate Gs proteins, and AKH I also potently activates Gq proteins. AKH I and - less effectively - AKH II accelerate spiking of DUM neurons via an increase of a pacemaking Ca2+ current. Systemically injected AKH I stimulates locomotion in contrast to AKH II. This behavioral difference corresponds to the different effectiveness of the AKHs on the level of G-proteins.
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PMID:Metabolic regulation and behavior: how hunger produces arousal - an insect study. 1822 Sep 52

Type 1 diabetes mellitus is classified as either autoimmune or idiopathic. Fulminant type 1 diabetes was originally reported as a subtype of idiopathic type 1 diabetes. Though involvement of viral infections has been suggested as a triggering mechanism, its pathogenesis remains unknown. Here, we present a case of fulminant type 1 diabetes associated with significant elevation of mumps titers. A 56-year-old Japanese man had suffered from nausea and generalized fatigue for two days before being transferred to our hospital in a confused state. Findings on admission revealed a high blood glucose level, near-normal HbA1c level, metabolic acidosis, and increased urinary ketone levels. Serum tests for islet-associated autoantibodies were negative. The serum, urinary C-peptide levels and the result of glucagon test indicated severe impairment of insulin secretion. These results were compatible with the diagnosis of fulminant type 1 diabetes. Also, he was suspected as having mumps infection on the basis of serological testing. These findings suggest that fulminant type 1 diabetes developed after mumps virus infection in our case. To the best of our knowledge, no other report has indicated an association between a recent mumps infection and the onset of fulminant type 1 diabetes. This case suggests an association between fulminant type 1 diabetes and mumps virus infection.
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PMID:A case of fulminant type 1 diabetes associated with significant elevation of mumps titers. 1852 Jan 3

Hypothalamic neuronal histamine and its H(1) receptor (H(1)-R), a leptin signaling pathway in the brain, regulate body weight and adiposity by affecting food intake and energy expenditure. Glucagon-like peptide-1 and/or corticotrophin-releasing hormone mediate leptin signaling to neuronal histamine. Leptin-induced suppression of food intake and upregulation of uncoupling protein-1 expression in brown adipose tissue were partially attenuated in histamine H(1)-R knockout (H(1)KO) mice. H(1)KO mice developed maturity-onset obesity. Hyperphagia and decreased energy expenditure assessed by the expression of uncoupling protein-1 mRNA were observed in older (48-wk-old) obese H(1)KO mice but not in younger (12-wk-old) non-obese H(1)KO mice. However, the diurnal feeding rhythm was impaired even in younger non-obese animals. Specifically, disruption of the feeding rhythm developed before the onset of obesity in H(1)KO mice. Correction of these abnormal feeding rhythms with scheduled feeding improved the obesity and associated metabolic disorders in the H(1)KO mice. These findings suggest that histamine H(1)-R is crucial for regulating the feeding rhythm and in mediating the effects of leptin. Early disruption of H(1)-R-mediated functions in H(1)KO mice may lead to hyperphagia and decreased energy expenditure, which may contribute to the development of obesity in these animals.
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PMID:Hypothalamic neuronal histamine regulates body weight through the modulation of diurnal feeding rhythm. 1872 79


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