Glucagon Research Papers - Academia.edu (original) (raw)

The subcellular localization of five isoforms of facilitated-diffusion glucose transporters (GLUTs), from GLUT1 to GLUT5, in rat pancreatic islets was studied by immunohistochemistry using rabbit polyclonal antisera against mouse or rat... more

The subcellular localization of five isoforms of facilitated-diffusion glucose transporters (GLUTs), from GLUT1 to GLUT5, in rat pancreatic islets was studied by immunohistochemistry using rabbit polyclonal antisera against mouse or rat GLUT peptides. Animals were perfusion-fixed with phosphate-buffered 4% paraformaldehyde and the pancreases were removed. Some specimens were embedded in paraffin, serially sectioned, and immunostained for glucagon, insulin, somatostatin, and the GLUTs for light microscopic observation. Others were prepared for immunoelectron microscopy by the post-embedding method. By these methods, GLUT2 immunostaining was observed on the lateral membranes of pancreatic beta-cells, whereas GLUT3 immunoreaction was predominantly localized in the cytoplasm of beta-cells and was not found in alpha-cells. In contrast, GLUT5 immunostaining was preferentially localized in the cytoplasm of alpha-cells compared to that of beta-cells. However, GLUT1 and GLUT4 were either barely or not at all detectable in any cells. These results suggest that rat islets take up glucose by at least three different processes and that blood glucose levels could be modulated differentially by: a high Km glucose transporter, GLUT2, in beta-cells; by a low Km glucose transporter, GLUT3, in beta-cells; and by a low Km glucose transporter, GLUT5, in alpha-cells.

Normal rats fed for 105 days on an experimental diet made up of standard laboratory chow supplemented with 0.5% of a mixture of brominated sunflower-olive oil (BVO) developed a significant increase in the triacylglycerol content of the... more

Normal rats fed for 105 days on an experimental diet made up of standard laboratory chow supplemented with 0.5% of a mixture of brominated sunflower-olive oil (BVO) developed a significant increase in the triacylglycerol content of the heart, liver and soleus muscle compared to controls. In addition, BVO-treated rats had a decrease in plasma levels of triacylglycerol and total and HDL cholesterol. Plasma fatty acid levels and plasma post-heparin lipolytic activities, such as H-TGL, LPL, T-TGL and MGH were similar to those of control animals fed the standard chow alone. Heart PDHa (active portion of pyruvate dehydrogenase) was dramatically decreased in the BVO-fed rats. A faster rate of spontaneous lipolysis was recorded in the isolated perfused preparation of hearts from the experimental animals. The addition of 10(-7) M of glucagon to the perfusate, however, revealed a lipolytic effect comparable to the one observed in the control rats. In summary, our findings of normal fatty acids and low triacylglycerol plasma levels associated with normal activities of the various PHLA (post-heparin lipolytic activity) enzymes suggest that accumulation of triacylglycerol in heart muscle may not be explained essentially in terms of an elevated uptake and/or increased delivery of plasma fatty acids or plasma triacylglycerol. A decreased in situ catabolism of tissue triacylglycerol also appears unlikely because the spontaneous as well as the glucagon induced lipolysis in the heart both were found to be unimpaired.(ABSTRACT TRUNCATED AT 250 WORDS)

The metabolic and hormonal changes during a standard physical exercise were studied in healthy subjects and in insulin-dependent diabetics well matched for body weight, and therefore submitted to a similar work load in a physiologic... more

The metabolic and hormonal changes during a standard physical exercise were studied in healthy subjects and in insulin-dependent diabetics well matched for body weight, and therefore submitted to a similar work load in a physiologic range, and in obese subjects that, owing to their weight, faced a significant heavier work in the same environmental conditions. Moderate work load did not lead to significant changes in metabolic and hormonal blood parameters (blood glucose, FFA and glycerol; insulin, glucagon, growth hormone and cortisol) in healthy subjects. A similar substrate homeostasis was seen in insulin-dependent diabetics, that however showed marked hormonal alterations. In these subjects, indeed, higher levels of plasma glucagon and GH were reached during work and in the recovery phase. Obese subjects, submitted to a heavier work load, presented a marked increase in blood glucose and glycerol which agrees with high GH and cortisol levels, and a subsequent increment of IRI which corresponds to a normalization of blood glucose and glycerol. Obese subjects, therefore, show a normal sensitivity to work load. Considerations about the work load in everyday life are discussed.

The influence of glucagon on glycaemic control in type 1 diabetes is debated. We investigated the relationship between postprandial glucagon levels and HbA1c during a period up to 60 months after diagnosis of childhood type 1 diabetes.... more

The influence of glucagon on glycaemic control in type 1 diabetes is debated. We investigated the relationship between postprandial glucagon levels and HbA1c during a period up to 60 months after diagnosis of childhood type 1 diabetes. The Danish remission phase cohort comprised 129 children (66 boys) with type 1 diabetes whose mean (SD) age at onset was 10.0 (3.9) years. Liquid mixed-meal tests were performed prospectively at 1, 3, 6 and 12 months and a subset of 40 patients completed follow-up at 60 months. Postprandial (90 min) plasma levels of glucagon, glucose (PG), C-peptide, total glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and HbA1c were analysed. Multivariate regression (repeated measurements with all five visits included) was applied and results expressed as relative change (95% CI). Postprandial glucagon levels increased 160% from 1 to 60 months after diagnosis (p < 0.0001). A doubling in postprandial PG corresponded to a 21% inc...

Several lines of evidence suggest that the endogenous opioid peptides endorphins may play a role in the defensive response of the organism to stress. The present paper summarizes these findings as well as evidence linking endorphins to... more

Several lines of evidence suggest that the endogenous opioid peptides endorphins may play a role in the defensive response of the organism to stress. The present paper summarizes these findings as well as evidence linking endorphins to the anterior pituitary polypeptide hormone adrenocorticotropin (ACTH). Evidence is presented that endorphins may function as trophic hormones in peripheral target organs such as the adrenal medulla and the pancreas. As such they may be part of the physiological mechanisms that mediate adrenaline and glucagon release in response to stress. Endorphins (enkephalins) are also suggested to play a role in the control of the pituitary gland during stress. In such capacity they may act as hormone-releasing or inhibiting factors. Finally, endorphins appear to play a role in the behavioral concomitants of stress. In such capacity endorphins are suggested to function as modulators of neural systems that mediate the elaboration and expression of the reactive/affe...

The secretion of glucagon by pancreatic α-cells plays a critical role in the regulation of glycaemia. This hormone counteracts hypoglycaemia and opposes insulin actions by stimulating hepatic glucose synthesis and mobilization, thereby... more

The secretion of glucagon by pancreatic α-cells plays a critical role in the regulation of glycaemia. This hormone counteracts hypoglycaemia and opposes insulin actions by stimulating hepatic glucose synthesis and mobilization, thereby increasing blood glucose concentrations. During the last decade, knowledge of α-cell physiology has greatly improved, especially concerning molecular and cellular mechanisms. In this review, we have addressed recent findings on α-cell physiology and the regulation of ion channels, electrical activity, calcium signals and glucagon release. Our focus in this review has been the multiple control levels that modulate glucagon secretion from glucose and nutrients to paracrine and neural inputs. Additionally, we have described the glucagon actions on glycaemia and energy metabolism, and discussed their involvement in the pathophysiology of diabetes. Finally, some of the present approaches for diabetes therapy related to α-cell function are also discussed in...

Glukagon adalah antagonis dari insulin: yang disekresi pada saat kadar gula darah dalam darah rendah. Pada prinsipnya menaikkan kadar gula di dalam darah. Dia diproduksi di sel alpha dari pankreas. Glukagon melewati dalam proses... more

Glukagon adalah antagonis dari insulin: yang disekresi pada saat kadar gula darah dalam darah rendah. Pada prinsipnya menaikkan kadar gula di dalam darah. Dia diproduksi di sel alpha dari pankreas. Glukagon melewati dalam proses sintesenya yang disebut sebagai limited proteolyse, yang artinya molekul glucagon berasal dari prohormon yang lebih tepatnya disebut sebagai prohormon. Gen untuk glukagon selain di pankreas juga terdapat di otak dan sel enteroendokrin L di sistem pencernaan (Ileum dan Kolon). Sumber : wikipedia. Struktur primer dari Glukagon adalah yang terdiri dari 29 asam amino dan mempunyai massa molekul 3483 Da. His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser-Arg-Arg-Ala-Gln-Asp-Phe-Val-Gln-Trp-Leu-Met-Asn-Thr 1. Stimulus sekresi glukagon adalah kondisi hipoglisemia atau jika konsentrasi asam amino turun di dalam darah setelah konsumsi makanan yang kaya protein. Walaupun begitu konsumsi makanan yang kaya mengandung protein tidak hanya menstimulasi pengeluaran hormon glukagon tetapi juga hormon insulin. Hormon neurotransmiter sistem saraf autonom seperti Asetilkolin dan Adrenalin lewat pencerap ß2 juga menstimulasi pengeluaran hormon glukagon. Selain itu juga sederetan hormon berikut yang diciptakan di sistem pencernaan Gastrin, CCK, GIP, GH. 2. Inhibitor atau yang menghambat sekresi glukagon adalah kondisi hiperglisemia atau jika konsentrasi gula darah naik. Selanjutnya juga hormon insulin yang adalah antagonisnya, GHIH, GLP-1, GABA, Sekretin, dan waktu makan yang kaya kandungan karbohidrat Glucagon mempunyai efek yang berlawanan dengan insulin, yakni Lipolisis; penguraian lemak. Ini terjadi di jaringan lemak Proteolisis; penguraian protein. Ini terjadi di otot Gluconeogenesis dan Glykogenolisis; membuat glukosa. Ini terjadi di hati NaCl-, Kalsium-, dan Magnesiumresorption. Ini terjadi di bagian yang naik dan gemuk dari Henle tubulus yakni ginjal. Apabila hormon glukagon diikat pada sebuah reseptor (hormon-Reseptor komplex), maka dia mengakibatkan kenaikan konsentrasi cAMP atau second messenger di dalam sel reseptor. Di jaringan lemak lemak akan diuraikan lewat enzym lipase akan menjadi Gliserol selanjutnya dibawa ke hati untuk Glukoneogenesis. Di adypozyt atau sel lemak Adrenalin atau Noradrenalin juga menstimulasi lipolisis lewat ß3 reseptor. Pada individu yang kekurangan hormon insulin seperti pada keadaan lapar atau Diabetes militus jaringan lemak menjadi lebih sensitif dengan rangsangan adrenerge-noradrenerg hormon dan juga hormon cortisol. Artinya jaringan lemak mengekspresikan rezeptor ß3 lebih banyak di permukaan selnya begitu pula dengan reseptor buat hormon cortisol. Logikanya adalah lemak merupakan sumber energi penting bagi individu dalam keadaan lapar atau diabetes militus, jika tubuh tidak dapat menghasilkan energi dari glukosa.

One of the hallmarks of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a drastically reduced feed intake by an unknown mechanism. To further elucidate this wasting syndrome, we followed the effects of a single large... more

One of the hallmarks of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a drastically reduced feed intake by an unknown mechanism. To further elucidate this wasting syndrome, we followed the effects of a single large dose (100 μg/kg) of TCDD on the serum levels of several energy balance-influencing hormones, clinical chemistry variables, and hepatic aryl hydrocarbon receptor (AHR) expression in two rat strains that differ widely in their TCDD sensitivities, for up to 10 days. TCDD affected most of the analytes in sensitive Long-Evans rats, while there were few alterations in the resistant Han/Wistar strain. However, analyses of feed-restricted unexposed Long-Evans rats indicated several of the perturbations to be secondary to energy deficiency. Notable increases in ghrelin and glucagon occurred in TCDD-treated Long-Evans rats alone, which links these hormones to the wasting syndrome. The newly found energy balance regulators, insulin-like growth factor 1 and fibr...

The glucokinase gene is expressed not only in pancreatic B cells and in the liver, but also in pancreatic alpha cells, and in some cells of the central nervous system. A decreased glucokinase activity in the latter cell types may... more

The glucokinase gene is expressed not only in pancreatic B cells and in the liver, but also in pancreatic alpha cells, and in some cells of the central nervous system. A decreased glucokinase activity in the latter cell types may interfere with counterregulatory responses to hypoglycemia. In order to assess functional consequences of glucokinase mutations, counterregulatory hormones secretion and glucose production (6,6(- 2) H glucose) were monitored during an hyperinsulinemic clamp at about 2.4 pmol.kg(- 1).min(- 1) insulin with progressive hypoglycemia in 7 maturity onset diabetes of the young (MODY) type 2 patients, 5 patients with type 2 diabetes, and 13 healthy subjects. Basal glucose concentrations were significantly higher in MODY2 patients (7.6 +/- 0.4 mmol.l(- 1) ) and type 2 diabetic patients (12.4 +/- 2.3 mmol.l(- 1) ) than in healthy subjects (5.3 +/- 0.1 mmol.l(- 1), p&lt;0.01) but counterregulatory hormones concentrations were identical. Insulin-mediated glucose disposal and suppression of endogenous glucose production at euglycemia were unchanged in MODY2 patients, but were blunted in type 2 diabetes. During progressive hypoglycemia, the glycemic thresholds of MODY2 patients for increasing glucose production (5.0 +/- 0.4 mmol.l(- 1) ) and for glucagon stimulation (4.5 +/- 0.4 mmol. l(- 1) ) were higher than those of healthy subjects and type 2 diabetic patients (3.9 +/- 0.1 and 4.1 +/- 0.1 mmol.l(- 1) respectively for glucose production and 3.7 +/- 0.1 and 3.5 +/- 0.1 mmol.l(- 1) for glucagon stimulation, p &lt;0.02 in both cases). These results indicate that counterregulatory responses to hypoglycemia are activated at a higher plasma glucose concentration in MODY2 patients. This may be secondary to decreased glucokinase activity in hypothalamic neuronal cells, or to alterations of glucose sensing in pancreatic alpha cells and liver cells.

Splanchnic and systemic arteriolar vasodilationplays an important role in ascites formation incirrhosis. Octreotide produces splanchnicvasoconstriction, but the effects on systemichemodynamics and renal function are controversial. This... more

Splanchnic and systemic arteriolar vasodilationplays an important role in ascites formation incirrhosis. Octreotide produces splanchnicvasoconstriction, but the effects on systemichemodynamics and renal function are controversial. This studyevaluated the effect of subcutaneous octreotideadministration on systemic hemodynamics, endogenousvasoactive systems, and renal function in cirrhoticpatients with ascites. Twenty patients were included: 10received octreotide 250 μg/12 hr subcutaneously (forfive days), and 10 did not. No statistically significantchanges were found in mean arterial pressure and cardiac rate. Octreotide induced astatistically significant decrease in plasma reninactivity (P < 0.01), plasma aldosterone (P = 0.01)and plasma glucagon (P < 0.05). No significantvariations were observed in other systemic vasoactivesubstances (nitric oxide and prostacyclin). Renalfunction was not modified in either group. Inconclusion, in cirrhotic patients with ascites,subcutaneous octreotide administration decreases plasma glucagon, reninactivity, and aldosterone without changing in systemichemodynamics or renal function.

Automated and manual deprotection methods for allyl/allyloxycarbonyl (Allyl/Alloc) were evaluated for the preparation of side-chain-to-side-chain cyclic peptides. Using a standard Allyl/Alloc deprotection method, a small library of cyclic... more

Automated and manual deprotection methods for allyl/allyloxycarbonyl (Allyl/Alloc) were evaluated for the preparation of side-chain-to-side-chain cyclic peptides. Using a standard Allyl/Alloc deprotection method, a small library of cyclic peptides with lactam bridges (with seven amino acids) was prepared on an automatic peptide synthesizer. We demonstrate that the Guibe method for removing Allyl/Alloc protecting groups under specific neutral conditions [Pd(PPh3)4/PhSiH3)/DCM] can be a useful, efficient and reliable method for preparing long cyclic peptides on a resin. We have also manually synthesized a cyclic glucagon analogue containing 24 amino acid residues. These results demonstrated that properly controlled palladium-mediated deprotection of Allyl/Alloc protecting groups can be used to prepare cyclic peptides on the resin using an automated peptide synthesizer and cyclic peptides with a long chain.

The activity of liver branched-chain 2-oxo acid dehydrogenase complex was measured in rats fed on low-protein diets and given adrenaline, glucagon, insulin or dibutyryl cyclic AMP in vivo. Administration of glucagon or adrenaline (200... more

The activity of liver branched-chain 2-oxo acid dehydrogenase complex was measured in rats fed on low-protein diets and given adrenaline, glucagon, insulin or dibutyryl cyclic AMP in vivo. Administration of glucagon or adrenaline (200 micrograms/100 g body wt.) resulted in a 4-fold increase in the percentage of active complex. As with glucagon and adrenaline, treatment of rats with cyclic AMP (5 mg/100 g body wt.) resulted in marked activation of branched-chain 2-oxo acid dehydrogenase. Insulin administration (1 unit/100 g body wt.) also resulted in activation of enzyme; however, these effects were less than those observed with glucagon and adrenaline. In contrast with the results obtained with low-protein-fed rats, administration of adrenaline (200 micrograms/100 g body wt.) to rats fed with an adequate amount of protein resulted in only a modest (14%) increase in the activity of the complex. The extent to which these hormones activate branched-chain 2-oxo acid dehydrogenase appear...

Diabetes is generally divided into the categories ‘type 1 diabetes’ and ‘type 2 diabetes’. They have much in common with each other, but differ in the cause and urgency of treatment necessary (see Table 1.1). As a broad generalization,... more

Diabetes is generally divided into the categories ‘type 1 diabetes’ and ‘type 2 diabetes’. They have much in common with each other, but differ in the cause and urgency of treatment necessary (see Table 1.1). As a broad generalization, type 1 diabetes occurs in those who are generally younger, so children and teenagers are more likely to have type 1 diabetes, and those in middle age type 2. It is also true that those with type 1 diabetes are generally of normal weight, while overweight is common in those with type 2. It is certain that overweight is a risk for type 2 diabetes, and not for type 1.

We previously reported that a eucaloric, low fat, liquid formula diet enriched in simple carbohydrate markedly increased the synthesis of fatty acids in lean volunteers. To examine the diet sensitivity of obese subjects, 7 obese and 12... more

We previously reported that a eucaloric, low fat, liquid formula diet enriched in simple carbohydrate markedly increased the synthesis of fatty acids in lean volunteers. To examine the diet sensitivity of obese subjects, 7 obese and 12 lean volunteers were given two eucaloric low fat solid food diets enriched in simple sugars for 2 weeks each in a random-order, cross-over design (10% fat, 75% carbohydrate vs. 30% fat, 55% carbohydrate, ratio of sugar to starch 60:40). The fatty acid compositions of both diets were matched to the composition of each subject's adipose tissue and fatty acid synthesis measured by the method of linoleate dilution in plasma VLDL triglyceride. In all subjects, the maximum % de novo synthesized fatty acids in VLDL triglyceride 3;-9 h after the last meal was higher on the 10% versus the 30% fat diet. There was no significant difference between the dietary effects on lean (43+/-13 vs. 12+/-13%) and obese (37+/-15 vs. 6+/-6%) subjects, despite 2-fold eleva...

Glucagon-(1–21)-peptide, the peptide containing the amino acid sequence (1–21) of glucagon, has the same spasmolytic effect as the complete molecule, without its metabolic action. The effect of glucagon and glucagon-(1–21)-peptide on... more

Glucagon-(1–21)-peptide, the peptide containing the amino acid sequence (1–21) of glucagon, has the same spasmolytic effect as the complete molecule, without its metabolic action. The effect of glucagon and glucagon-(1–21)-peptide on sphincter of Oddi motor activity was evaluated in 20 patients undergoing ERCP and endoscopic biliary manometry. Glucagon produced a nonsignificant decrease in basal pressure, but significantly reduced both frequency and amplitude of phasic activity of the sphincter of Oddi. Glucagon-(1–21)-peptide showed no effect on basal pressure and amplitude of phasic activity, but provoked a significant reduction of frequency of phasic contraction.

Exercise-induced alterations in the concentrations of plasma glucagon-like immunoreactivity (GLI), plasma free fatty acids (FFA) and blood glucose and lactate were measured in separate groups of male and female domestic fowl. There were... more

Exercise-induced alterations in the concentrations of plasma glucagon-like immunoreactivity (GLI), plasma free fatty acids (FFA) and blood glucose and lactate were measured in separate groups of male and female domestic fowl. There were only small changes in blood glucose and lactate concentrations but plasma FFA and GLI rose by up to 450 and 200% respectively. There was evidence that the GLI response was stronger at higher exercise intensities. It is suggested that the mobilization of FFA for use as energy substrates by the working muscles may be stimulated by the enhanced secretion of glucagon.