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

Using a bivascularly perfused rat liver, we investigated the hepatic extraction and hepatic action on glucose output of insulin, glucagon, and epinephrine. The liver was perfused for 70 min without recirculation via the portal vein and hepatic artery (3.0 ml/(min.g liver) from portal vein and 1.0 ml/(min.g liver) from celiac artery). Low and high concentration of insulin, glucagon, or epinephrine (450 and 4,500 pM, 21.5 and 215 pM, or 410 and 4,100 pM, respectively) was added to the perfusing medium via portal vein (P-liver), via celiac artery (H-liver), or via portal vein and celiac artery (H-P-liver). Hepatic extraction of insulin, glucagon, or epinephrine was not significantly different among H- (56 +/- 9 and 21 +/- 5%, 31 +/- 7 and 24 +/- 6%, or 22 +/- 8 and 17 +/- 5%), P- (50 +/- 10 and 23 +/- 6%, 32 +/- 9 and 23 +/- 7%, or 22 +/- 9 and 18 +/- 6%), and H-P-liver (55 +/- 11 and 24 +/- 6%, 30 +/- 9 and 26 +/- 8%, or 20 +/- 9 and 17 +/- 6%). Glucagon- or epinephrine-induced increase in glucose output was also similar in H- (245 +/- 47 and 498 +/- 82 mumol/30 min, or 112 +/- 21 and 215 +/- 38 mumol/30 min), P- (258 +/- 51 and 512 +/- 95 mumol/30 min, or 128 +/- 20 and 220 +/- 36 mumol/30 min), and H-P-liver (263 +/- 58 and 515 +/- 94 mumol/30 min, or 129 +/- 22 and 225 +/- 39 mumol/30 min).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Hepatic extraction and hepatic action of insulin, glucagon, and epinephrine in bivascularly perfused rat liver. 823 Aug 56

To investigate the role of sympathoadrenergic activity on glucose production (Ra) during exercise, eight healthy males bicycled 20 min at 41 +/- 2 and 74 +/- 4% maximal O2 uptake (VO2max; mean +/- SE) either without (control; Co) or with blockade of sympathetic nerve activity to liver and adrenal medulla by local anesthesia of the celiac ganglion (Bl). Epinephrine (Epi) was in some experiments infused during blockade to match (normal Epi) or exceed (high Epi) Epi levels during Co. A constant infusion of somatostatin and glucagon was given before and during exercise. At rest, insulin was infused at a rate maintaining euglycemia. During intense exercise, insulin infusion was halved to mimic physiological conditions. During exercise, Ra increased in Co from 14.4 +/- 1.0 to 27.8 +/- 3.0 mumol.min-1.kg-1 (41% VO2max) and to 42.3 +/- 5.2 (74% VO2max; P < 0.05). At 41% VO2max, plasma glucose decreased, whereas it increased during 74% VO2max. Ra was not influenced by Bl. In high Epi, Ra rose more markedly compared with control (P < 0.05), and plasma glucose did not fall during mild exercise and increased more during intense exercise (P < 0.05). Free fatty acid and glycerol concentrations were always lower during exercise with than without celiac blockade. We conclude that high physiological concentrations of Epi can enhance Ra in exercising humans, but normally Epi is not a major stimulus. The study suggests that neither sympathetic liver nerve activity is a major stimulus for Ra during exercise. The Ra response is enhanced by a decrease in insulin and probably by unknown stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Regulation of hepatic glucose production during exercise in humans: role of sympathoadrenergic activity. 836 97

To clarify the physiological role of vagal amino acid sensors in the liver, the effect of hepatic vagotomy and/or celiac vagotomy (sectioning of the hepatic branch and/or the celiac branches of the vagus nerve) on the secretion of insulin and glucagon after intraperitoneal injection of neutral (L-alanine, L-leucine, and L-phenylalanine), acidic (L-glutamate), or nonmetabolized (cycloleucine) acids, was examined in rats. Hepatic vagotomy enhanced both plasma glucose and glucagon concentrations after intraperitoneal injection of alanine more than those in sham-vagotomized (control) rats, while after intraperitoneal injection of leucine, hepatic vagotomy decreased plasma glucose concentrations and enhanced plasma insulin concentrations more than in control animals. These effects, following both alanine and leucine administration, were blocked by celiac vagotomy. Glutamate, phenylalanine, and cycloleucine stimulation in hepatic-vagotomized rats caused no significant differences in plasma glucose, insulin, or glucagon levels as compared to those in sham-vagotomized rats. Celiac vagotomy alone did not affect plasma glucose, insulin, or glucagon concentrations after stimulation by these five amino acids. The physiological role of alanine and leucine sensors may be to prevent amino acid-induced exaggerated pancreatic hormone secretion and to maintain blood glucose homeostasis, while glutamate, phenylalanine, and cycloleucine have no effect on this pancreatic neuroendocrine system.
 ...
PMID:Hepatic vagal amino acid sensors modulate amino acid induced insulin and glucagon secretion in the rat. 845 96

To determine whether galanin is a pancreatic sympathetic neurotransmitter regulating insulin secretion in the baboon, as it is in the dog, we evaluated galanin for inhibitory effects on insulin secretion in conscious baboons, determined if baboon pancreatic islets are innervated by galaninergic fibers using immunohistochemistry, and measured galanin content in the major sympathetic ganglion supplying the pancreas. Surprisingly, infusion of galanin (1 microgram/kg per min) had no effect on arginine-stimulated secretion of either insulin (71 +/- 14 vs. 88 +/- 17 microU/ml; P = NS) or glucagon (104 +/- 12 vs. 94 +/- 9 pg/ml; P = NS). By contrast, growth hormone secretion was markedly increased during galanin infusion. In the baboon celiac ganglion, no galanin immunoreactivity was detectable in sympathetic neuronal cell bodies by immunostaining and their content of galanin-like immunoreactivity, determined by radioimmunoassay, was only 3% of that in dog celiac ganglion (5.2 +/- 0.8 vs. 158 +/- 13 pmol/g; P < 0.001). By contrast, galanin immunoreactivity was observed in many nerve fibers in the baboon exocrine pancreas and occasionally in baboon pancreatic islets. Moreover, galanin content of the baboon pancreas was similar to that of dog (8.7 +/- 1.5 vs. 5.5 +/- 1.2 pmol/g; P = NS). The finding of galanin immunoreactivity in many neuronal cell bodies in baboon intrapancreatic ganglia suggests a parasympathetic source for these galaninergic fibers in the baboon. Together these data demonstrate that galanin is likely to be a parasympathetic neurotransmitter in the baboon pancreas, without major effects on insulin or glucagon secretion.
 ...
PMID:Evidence that galanin is a parasympathetic, rather than a sympathetic, neurotransmitter in the baboon pancreas. 895 79

The purpose of this study was to determine whether section of the celiac branch of the vagus nerve in man affects the insulin response to intravenous glucagon injection. Patients who received a subtotal gastrectomy with lymph node dissection for gastric carcinoma were divided into two groups: the celiac-preserved group (n = 16) and the celiac-sectioned group (n = 13). The hepatic branches of the vagus were preserved in both groups. The glucagon test was performed twice in each patient during the operation; before and after manipulation of the celiac branch. Blood samples were collected just before and 6 min after the injection. No difference in the mean increases in blood glucose, insulin and C-peptide levels were seen between the two groups before the nerve manipulation. In the celiac-preserved group, the glucagon stimulated glucose-related C-peptide ratio (x 10(-3) was 0.5 +/- 0.7 before the nerve manipulation and 3.5 +/- 3.0 after it, a significant difference (p < 0.01). In the celiac-sectioned group, this increase was not observed, the ratio was 0.7 +/- 0.6 before the nerve manipulation and 0.8 +/- 3.4 after. These results indicate that the vagal celiac branch in man may also be involved in the control of pancreatic insulin release.
 ...
PMID:Section of the vagal celiac branch in man reduces glucagon-stimulated insulin release. 918 84

To evaluate the effect of bradykinin (BK) on rat islet alpha, beta, and delta cells, the rat pancreas was perfused in situ with BK (1 mumol/L) for 30 minutes via a cannula placed in the celiac artery. Insulin, glucagon, and somatostatin concentrations in the effluent were measured to determine the effect of BK on the secretion of these hormones. The BK concentration of the rat pancreas was also measured. Basal secretion of insulin, glucagon, and somatostatin in medium containing 6 mmol/L glucose was maintained at 6.5 +/- 0.5 ng/mL 124 +/- 8 pg/mL, and 511 +/- 22 pg/mL (n = 12), respectively. BK (1 mumol/L) induced a transient peak that was 3.7-fold of the baseline concentration within 3 minutes, followed by a sustained level that was approximately 50% higher than baseline. BK also transiently increased glucagon secretion with a peak that was 1.7-fold of the baseline concentration within 3 minutes, without a sustained secretion phase. BK caused a reduction in somatostatin secretion within 3 minutes to a level of 60% to 70% of the baseline concentration. The BK concentration of the rat pancreas was 3.42 +/- 1.45 micrograms/g protein (n = 5), which was approximately 3 mumol/L. We concluded that BK stimulated insulin secretion, transiently increased glucagon secretion, and decreased somatostatin secretion during the 30-minute perfusion of the rat pancreas.
 ...
PMID:The effect of bradykinin on secretion of insulin, glucagon, and somatostatin from the perfused rat pancreas. 932 91

Necrolytic migratory erythema is characterized by waves of irregular erythema in which a central bulla develops, and subsequently erodes and becomes crusted. It usually occurs in patients with an alpha-islet cell tumor of the pancreas. However, necrolytic migratory erythema has also been observed in patients without an associated glucagonoma. We describe a woman with iatrogenic necrolytic migratory erythema. She received intravenous glucagon for hypoglycemia associated with an insulin-like growth factor II-secreting hemangiopericytoma. After chemotherapy, she developed necrolytic migratory erythema. The characteristics of the previously reported patients with nonglucagonoma-associated necrolytic migratory erythema are reviewed. In patients with nonglucagonoma-associated necrolytic migratory erythema, the dermatosis-related conditions most commonly observed were celiac disease or malabsorption, cirrhosis, malignancy, and pancreatitis; less common conditions included hepatitis, inflammatory bowel disease, heroin abuse, and odontogenic abscess. Although the pathogenesis of necrolytic migratory erythema remains unknown, hyperglucagonemia appears to have had a causative role in the development of this dermatosis in our patient. Patients who develop necrolytic migratory erythema should be evaluated for the presence of a glucagonoma; if a glucagonoma is ruled out, evaluation for other conditions known to occur with necrolytic migratory erythema, such as liver disease, malabsorptive disorders, and nonislet-cell tumors is warranted.
 ...
PMID:Iatrogenic necrolytic migratory erythema: a case report and review of nonglucagonoma-associated necrolytic migratory erythema. 959 6

Plasma levels of glucagon-like peptide-1 (GLP-1) rise rapidly after nutrient ingestion, suggesting the existence of a proximal gut signal regulating GLP-1 release from the L cells of the distal small intestine. Glucose-dependent insulinotropic peptide (GIP) has been shown to be one such proximal signal; however, the dependence of GIP on gastrin-releasing peptide, a neuromodulator, suggested a role for the nervous system in this proximal-distal loop. Investigations into the nature of this proximal signal were therefore conducted in an in situ model of the rat gastrointestinal system. Infusions of corn oil into a 10-cm segment of duodenum that was isolated by loose ligation (to ensure that the luminal contents did not progress to the ileal L cell) increased the secretion of GLP-1 in parallel with that of gut glucagon-like immunoreactivity (gGLI; r = 0.85; P < 0.05). Infusion of fat into a transected segment of duodenum also significantly raised gGLI secretion compared with saline infusion, reaching a peak value of 132 +/- 37 pg/ml above basal (P < 0.05). However, peak secretion was significantly delayed when the gut was transected compared with that after ligation alone (19 +/- 4 vs. 6 +/- 1 min, respectively; P < 0.05). Furthermore, bilateral subdiaphragmatic vagotomy in conjunction with gut transection completely abolished the fat-induced rise in gGLI secretion (P < 0.001). Consistent with a role for the vagus in the regulation of the L cell, stimulation of the distal end of the celiac branch of the subdiaphragmatic vagus nerve significantly stimulated the secretion of gGLI to a level of 71 +/- 14 pg/ml above basal (P < 0.05). As found previously, supraphysiological infusion of GIP significantly increased gGLI secretion in control animals by 123 +/- 32 pg/ml (P < 0.05); this was not prevented by hepatic branch vagotomy (96 +/- 25 pg/ml; P < 0.05). In contrast, although infusion of GIP at physiological levels into sham-vagotomized animals also increased gGLI secretion, by 40 +/- 6 pg/ml (P < 0.05), selective hepatic branch vagotomy abolished GIP-induced gGLI secretion (P < 0.05). The results of these experiments therefore demonstrate that the secretion of GLP-1 and gGLI from the ileal L cell in response to fat is regulated by a complex neuroendocrine loop, involving the enteric nervous system, the afferent and efferent vagus nerves, as well as the duodenal hormone GIP.
 ...
PMID:Role of the vagus nerve in mediating proximal nutrient-induced glucagon-like peptide-1 secretion. 1009 4

Generally, it is considered that visceral fat brings insulin resistance and hyper-insulinemia, in the mechanisms of metabolic syndromes. However, whether hyperinsulinemia brings about accumulation of visceral fat is not clear. We followed a case of insulinoma that caused primary hyperinsulinemia, and measured the change in visceral fat and insulin resistance before and after surgical resection of the insulinoma. A 58-year-old woman was admitted to investigate the cause of spontaneous hypoglycemia. An oral glucose tolerance test (OGTT) showed hyperinsulinemia with a high basal level and a glucagon infusion test showed an abnormally high insulin level. Abdominal computed tomography (CT) scan showed an accumulation of visceral fat. Selective celiac angiography showed a pancreatic tumor shadow. Under a diagnosis of insulinoma, the pancreatic body and tail were removed. At 3 months after the operation, the visceral fat area had decreased from 132.6 to 64.2 cm(2). The fasting serum total cholesterol and triglyceride were also reduced. In addition, high-density lipoprotein cholesterol and preheparin serum lipoprotein lipase mass had increased. The midband on the polyacrylamide gel disc electrophoresis of lipoproteins, which appeared before operation, had disappeared completely. An OGTT showed a non-diabetic pattern after the operation. These results suggest that hyperinsulinemia might be one of the factors that enhance visceral adiposity and insulin resistance.
 ...
PMID:Reduction of visceral adiposity after operation in a subject with insulinoma. 1535 80

After receiving information from afferent nerves, the hypothalamus sends signals to peripheral organs, including the liver, to keep homeostasis. There are two ways for the hypothalamus to signal to the peripheral organs: by stimulating the autonomic nerves and by releasing hormones from the pituitary gland. In order to reveal the involvement of the autonomic nervous system in liver function, we focus in this study on autonomic nerves and neuroendocrine connections between the hypothalamus and the liver. The hypothalamus consists of three major areas: lateral, medial, and periventricular. Each area has some nuclei. There are two important nuclei and one area in the hypothalamus that send out the neural autonomic information to the peripheral organs: the ventromedial hypothalamic nucleus (VMH) in the medial area, the lateral hypothalamic area (LHA), and the periventricular hypothalamic nucleus (PVN) in the periventricular area. VMH sends sympathetic signals to the liver via the celiac ganglia, the LHA sends parasympathetic signals to the liver via the vagal nerve, and the PVN integrates information from other areas of the hypothalamus and sends both autonomic signals to the liver. As for the afferent nerves, there are two pathways: a vagal afferent and a dorsal afferent nerve pathway. Vagal afferent nerves are thought to play a role as sensors in the peripheral organs and to send signals to the brain, including the hypothalamus, via nodosa ganglia of the vagal nerve. On the other hand, dorsal afferent nerves are primary sensory nerves that send signals to the brain via lower thoracic dorsal root ganglia. In the liver, many nerves contain classical neurotransmitters (noradrenaline and acetylcholine) and neuropeptides (substance P, calcitonin gene-related peptide, neuropeptide Y, vasoactive intestinal polypeptide, somatostatin, glucagon, glucagon-like peptide, neurotensin, serotonin, and galanin). Their distribution in the liver is species-dependent. Some of these nerves are thought to be involved in the regulation of hepatic function as well as of hemodynamics. In addition to direct neural connections, the hypothalamus can affect metabolic functions by neuroendocrine connections: the hypothalamus-pancreas axis, the hypothalamus-adrenal axis, and the hypothalamus-pituitary axis. In the hypothalamus-pancreas axis, autonomic nerves release glucagon and insulin, which directly enter the liver and affect liver metabolism. In the hypothalamus-adrenal axis, autonomic nerves release catecholamines such as adrenaline and noradrenaline from the adrenal medulla, which also affects liver metabolism. In the hypothalamus-pituitary axis, release of glucocorticoids and thyroid hormones is stimulated by pituitary hormones. Both groups of hormones modulate hepatic metabolism. Taken together, the hypothalamus controls liver functions by neural and neuroendocrine connections.
 ...
PMID:Neural connections between the hypothalamus and the liver. 1538 20


<< Previous 1 2 3 4 5 6 Next >>