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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a continuation of our studies on the mechanism of central nervous system induced hyperglycemia in the rat, we evaluated the relative contribution of a direct neural effect on the liver and of certain hormones to the hyperglycemia induced by administration of thyrotropin-releasing hormone (TRH). The findings were compared with those of a previous investigation using neostigmine or 2-deoxy-D-glucose. In the present study TRH was injected into the third cerebral ventricle of rats, and the concentrations of hepatic venous plasma glucose, immunoreactive glucagon, immunoreactive insulin, epinephrine, and norepinephrine, were measured. Four groups of animals were evaluated: (1) intact rats; (2) rats receiving an infusion of somatostatin with insulin via the femoral vein to inhibit glucagon secretion and to maintain the basal insulin level; (3) rats bilaterally adrenalectomized (ADX) to prevent epinephrine secretion, and (4) ADX rats administered an infusion of somatostatin and insulin. Evaluation of the areas under the glucose curves for the rats receiving somatostatin with insulin, ADX rats, and ADX rats receiving somatostatin with insulin showed values 202, 50, and 79% of those observed in intact animals. These observations suggest that TRH-induced hyperglycemia results from at least two effects: a direct neural effect on the liver including a suppressive effect of epinephrine on insulin secretion (contributing about 79% to the total hyperglycemic effect) and a direct effect of epinephrine on the liver (contributing about 21% to the total hyperglycemic effect).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relative contribution of nervous system and hormones to hyperglycemia induced by thyrotropin-releasing hormone in fed rats. 168 38

Recent results have demonstrated altered corticotropin-releasing factor (CRF)-41 content of the neurointermediate lobe (NIL) of the pituitary gland in response to various manipulations including osmotic stimulation. This study was undertaken to determine whether changes in CRF-41 content of the NIL are accompanied by changes in intensity of CRF-41-like immunoreactivity (CRF-41-LI) of neurosecretory neurones of the hypothalamus in response to osmotic stimulation. Wistar rats of both sexes given either tap water ad libitum, 2% NaCl solution, or access to tap water was limited to 20 min daily, for 7 days. Subsets of rats from each group were adrenalectomized (ADX) or treated with dexamethasone (DEX). Thirty-six hour before perfusion with fixative consisting of buffered formaldehyde and picric acid, animals received 75 micrograms colchicine i.c.v. Forty micrometer thick vibratome sections were stained for CRF-LI, arginine vasopressin (AVP-LI) and oxytocin (OXY-LI) using the avidin-biotin-peroxidase complex method. In response to both types of osmotic stimulation magnocellular neurones of the paraventricular (PVN) and supraoptic nuclei (SON) showed increased CRF-LI, AVP-LI and OXY-LI, while CRF-LI of parvocellular perikarya of the PVN decreased. The enhanced CRF-LI seemed to appear in a subset of magnocellular neurones with OXY-LI but not AVP-LI. Increased staining intensities were also observed in magnocellular neurones in ADX rats challenged osmotically. In contrast, systemic DEX administration, as well as implantation of DEX in the area on the SON, sharply attenuated CRF-LI but not AVP-LI or OXY-LI of magnocellular neurones in osmotically stimulated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxytocinergic neurons in rat hypothalamus. Dexamethasone-reversible increase in their corticotropin-releasing factor-41-like immunoreactivity in response to osmotic stimulation. 211 29

We previously reported that neostigmine injected into the third cerebral ventricle stimulated adrenal secretion of epinephrine, secretion of glucagon from the pancreas, and direct neural innervation of the liver, resulting in hepatic venous plasma hyperglycemia in anesthetized fed rats. However, receptor type of these 3 mechanisms is not known. Therefore, we examined the effects of intraventricularly injected cholinergic or adrenergic antagonists on neostigmine-induced catecholamines in intact rats, glucagon secretion which is mediated by direct neural innervation of pancreas in bilateral adrenalectomized (ADX) rats, and hepatic venous hyperglycemia which is mediated by direct neural innervation of liver in ADX rats receiving constant infusion of somatostatin from femoral vein. Atropine injected into the third cerebral ventricle suppressed epinephrine secretion and dose-dependently inhibited hepatic venous hyperglycemia induced by neostigmine in intact rats. The neostigmine-induced glucagon secretion which occurs in ADX rats was suppressed by atropine. Atropine also prevented the neostigmine-induced hyperglycemia in ADX rats receiving constant somatostatin infusion through femoral vein (ADX-Somato rats). On the other hand, phentolamine, propranolol and hexamethonium showed no significant inhibitory effect on neostigmine-induced hyperglycemia, epinephrine and glucagon secretion in intact rats, glucagon secretion in ADX rats, or hyperglycemia in ADX-Somato rats. These results suggest that neostigmine-induced epinephrine and glucagon secretion and increased hepatic glucose output stimulated by direct neural innervation to liver is mediated by central muscarinic receptor in fed rats.
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PMID:Neostigmine-induced hyperglycemia is mediated by central muscarinic receptor in fed rats. 233 69

We examined the relative contributions of hormones and nervous system to the total 2-deoxy-D-glucose (2-DG)-induced central nervous system-mediated hyperglycemia. 2-DG was injected into the third cerebral ventricle in the following four groups of rats, and hepatic venous plasma glucose, immunoreactive glucagon, immunoreactive insulin, epinephrine, and norepinephrine were measured: 1) intact rats; 2) intact rats receiving somatostatin with insulin infusion through the femoral vein to inhibit glucagon secretion and maintain the basal insulin level; 3) bilateral adrenalectomized (ADX) rats to prevent epinephrine secretion; and 4) ADX rats receiving somatostatin with insulin infusion. Comparing areas under glucose curves among the intact rats, those receiving somatostatin with insulin infusion, ADX rats, and ADX rats receiving somatostatin with insulin infusion, the area under the glucose curve was intact rats greater than intact rats receiving somatostatin with insulin infusion greater than ADX rats receiving somatostatin with insulin infusion greater than ADX rats. These results suggest that there are three distinct sympathetic nervous system responses to 2-DG-induced central nervous system-mediated hyperglycemia. 2-DG-induced hyperglycemia is not dependent on only one of those three systems, it is dependent on all of them. The relative potency of the factors to 2-DG-induced hyperglycemia increases in the following order: direct neural innervation of liver (including suppressive epinephrine action on insulin secretion), glucagon, and direct epinephrine action on liver.
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PMID:The relative importance of nervous system and hormones to the 2-deoxy-D-glucose-induced hyperglycemia in fed rats. 256 82

We assessed the response of the adrenergic receptor in pancreatic glucagon secretion to central nervous system stimulation. Injection of neostigmine (5 x 10(-8) mol) into the third cerebral ventricle in intact rats resulted in increased epinephrine and norepinephrine secretion associated with glucagon secretion. This glucagon secretion was still observed in bilateral adrenalectomized (ADX) rats, although its concentration was significantly lower than that in the intact rats. This glucagon rise was significantly inhibited by ip treatment of ganglionic blocker with hexamethonium. Intraperitoneal injection of alpha-adrenergic receptor antagonist phentolamine (5 x 10(-7) mol), but not of beta-adrenergic receptor antagonist propranolol (1 x 10(-6) mol), reduced the hyperglucagonemic effect of a subsequent neostigmine injection in intact and ADX rats, although these antagonists did not influence epinephrine or norepinephrine secretion in intact rats. In addition, ip injection of the selective alpha 2-receptor antagonist yohimbine (5 x 10(-7) mol), but not of the selective alpha 1-receptor antagonist prazosin (1 x 10(-6) mol), inhibited the neostigmine-induced glucagon secretion in intact and ADX rats. From this evidence it is suggested that central nervous system-mediated glucagon release is enhanced by alpha 2-adrenoreceptor stimulation by either catecholamines or the autonomic nervous system.
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PMID:Central nervous system-mediated glucagon secretion is enhanced by alpha 2-adrenoreceptor activation. 256 93

Sucrose feeding has been shown previously to alter the plasma concentration of several factors which may regulate beta-adrenergic receptors, including corticosteroids and insulin as well as altered sympathetic nervous system (SNS) tone. For this reason we initiated a study of the effects of sucrose feeding on the beta-adrenergic receptor-adenylate cyclase system in rat liver plasma membranes. Beta-Adrenergic responsiveness was monitored by measuring isoproterenol stimulation of adenylate cyclase activity, while beta-adrenergic receptor characteristics were evaluated by analyzing [125I]iodocyanopindolol [( 125I]CYP) binding. Rats fed rat chow ad lib. supplemented by drinking water containing 10% sucrose solution exhibited a 50-75% reduction in hepatic isoproterenol-sensitive adenylate cyclase activity. This effect of sucrose was also observed in adrenalectomized (ADX) and 6-hydroxydopamine-pretreated animals, ruling out a causal role for corticosteroids or the sympathetic nervous system respectively. No effect was observed on basal, glucagon-, fluoride- or GTP-stimulated adenylate cyclase. A small but significant decrease in [125I]CYP specific binding capacity was observed in liver membranes prepared from sucrose-fed ADX rats, whereas no change in [125I]CYP binding capacity was observed in in sucrose-fed normal rats. These observations suggest that beta-receptor to adenylate cyclase coupling efficiency is decreased by the sucrose diet. The activities of two membrane-associated phospholipid methyltransferases and the content of endogenous S-adenosylmethionine in liver were reduced by sucrose feeding, implying a defect in the methylation pathway for phosphatidylcholine synthesis. The possible relationship between this latter finding and the observed decrease in beta-adrenergic receptor to adenylate cyclase coupling efficiency is discussed.
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PMID:Evidence for a decrease in the efficiency of beta-receptor coupling to adenylate cyclase in liver membranes from sucrose-fed rats. 298 31

The role of the exercise-induced increment in epinephrine was studied in five adrenalectomized (ADX) and in six normal dogs (C). Experiments consisted of an 80-min equilibration period, a 40-min basal period, and a 150-min exercise period. ADX were studied with epinephrine replaced to basal levels during rest and to increased levels during exercise to simulate its normal rise (HE) and on a separate day with epinephrine maintained at basal levels throughout the study (BE). Cortisol was replaced during rest and exercise in ADX so as to simulate the levels seen in C. Glucose was infused as needed in ADX to maintain the glycemia evident during exercise in C. Glucose production (Ra) and utilization (Rd) were assessed isotopically. In C, epinephrine had risen by 95 +/- 25 pg/ml by the end of exercise. In HE, the increment in epinephrine (117 +/- 29 pg/ml) was similar to that seen in C, whereas in BE epinephrine fell by 18 +/- 9 pg/ml. Basal norepinephrine levels were 139 +/- 9, 260 +/- 25, and 313 +/- 33 pg/ml in C, HE, and BE, respectively. In response to exercise, norepinephrine increased by nearly twofold in all protocols. Basal and exercise-induced changes in plasma glucagon and insulin were similar in C and ADX. Ra increased similarly in C (5.3 +/- 0.6 mg.kg-1.min-1) and HE (4.9 +/- 0.6 mg.kg-1.min-1). In BE, Ra rose normally for the initial 90 min but then declined resulting in a rise of only 2.9 +/- 0.5 mg.kg-1.min-1 after 150 min of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolic role of the exercise-induced increment in epinephrine in the dog. 305 3

The effect of zinc on serum glucose, insulin and glucagon as well as liver glycogen was investigated in normal, adrenalectomized (ADX), and diabetic rats. Serum glucose was significantly elevated within 15 minutes after intraperitoneal administration of zinc (25 mumol) but returned to normal limits within 4 hours. Similar effects on serum glucose were noted with orally administered zinc. Significant depletion of hepatic glycogen in zinc-treated rats suggests glycogenolysis was responsible at least in part for the increased blood glucose. Adrenalectomy completely eliminated the hyperglycemic response to this metal, whereas adrenergic blockade with phenoxybenzamine and propranolol was effective in preventing hyperglycemia. The hyperglycemic response to zinc was not eliminated in diabetic rats. Administration of dexamethasone, alone or in combination with zinc, was unable to change serum glucose concentrations in ADX rats. Plasma glucagon was significantly elevated within 15 minutes but was reduced 6 hours after zinc treatment. Insulin was significantly depressed within 30 minutes after administration of zinc and eventually increased over controls by 4 hours after treatment. These data suggest that the hyperglycemic response to zinc depends on a mechanism, requiring an intact adrenal gland, which acts to produce a rapid alteration in blood glucose.
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PMID:Hyperglycemic action of zinc in rats. 634 23

Insulin tolerance tests were carried out in normal subjects and in adrenalectomized (ADX) patients in order to better understand the importance of counter regulatory hormones for the recovery from hypoglycaemia. Compared to normal subjects recovery of plasma glucose and of free fatty acid levels in adrenalectomized patients is retarded. The levels of glucagon are significantly higher in ADX patients during rest than in normal subjects. As expected, epinephrine and norepinephrine levels did not increase in ADX patients and, accordingly, blood pressure did not change. Growth hormone levels were the same in both groups of subjects. Interestingly, there was no clear-cut difference with regard to subjective symptoms of hypoglycaemia. It would appear that epinephrine is important for the rapid initial recovery from hypoglycaemia, whereas other hormones play a more important role later on.
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PMID:Insulin hypoglycaemia in normal and adrenalectomized subjects: comparison of metabolic parameters and endocrine counter regulation. 702 15

The populations of endocrine cells in pancreatic islets are subjected to striking fluctuations in their size when subjected to sustained stimulation and/or inhibition of their secretory activity. The stimulation of a specific endocrine secretion is followed by proliferation of its producing cell, a situation that is reversed after interruption or inhibition of the stimulus. Morphometric and cytological modifications of somatostatin and glucagon producing cells (D and A cells respectively) in the islets of Langerhans have been studied by electron microscopy, immunocytochemistry and morphometry in pancreas of rats submitted to the following experimental conditions: 1) Adrenalectomized (ADX), 2) ADX treated with hydrocortisone, 3) Diabetic and 4) Cysteamine (CSH) treated rats. In addition to ultrastructural changes, the populations of A and D cells were analyzed morphometrically applying a computerized system for light microscopy of paraffin sections immunostained with peroxidase-antiperoxidase (PAP) technique. Glucagon cell population displayed striking alterations in fine structural features and in the volume density in the different experimental conditions examined. By contrast, the cytological organization and the size of somatostatin cell population were little or not affected except in the diabetic rats where the massive degeneration of beta cells grossly distorted the structure of the islets. These observations led to the conclusion that the population of D cells constitutes a stable of endocrine system, at variance to the profound modifications occurring in A cells when they are submitted to various experimental conditions that stimulate or inhibit their secretory activity.
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PMID:Differential proliferation of somatostatin and glucagon cells in rat pancreatic islets submitted to various stimuli. 759 19


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