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)

Pancreatic polypeptide (PP) levels of plasma and pancreas were studied in the rat after streptozotocin (STZ) injection. In 4 weeks of observation, plasma PP was elevated up to 4 times the control values with marked hyperglycemia and insulinopenia. At 4 weeks, intravenous (i.v.) glucose tolerance tests and i.v. insulin tolerance tests were performed. In the glucose tolerance test, control rats responded with a 10-fold increase in plasma insulin and 15% decrease in plasma PP levels, whereas STZ-diabetic rats produced no increase of plasma insulin and an approximately 50% reduction of plasma PP levels with marked hyperglycemia. In the insulin tolerance test, diabetic rats showed a marked increase in plasma PP levels and less increase in plasma insulin levels than the controls. In diabetic rats, pancreatic insulin levels were reduced to about 3.5% of control, whereas those of somatostatin (SRIF), PP and glucagon were elevated to 8.3, 2.7 and 1.4 times control, respectively. In a morphometric study, islet areas of diabetic rats were seen to be reduced to about 10% of control. With in vitro perfused pancreatic slices, STZ-diabetic pancreas released much more glucagon and PP than control pancreas. Thus, STZ injection in the rat caused marked beta-cell damage as well as hyperplasia of SRIF, PP and glucagon cells, with glucagon and PP hypersecretion.
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PMID:Pancreatic hormones in streptozotocin-diabetic rats. 289 Jun 93

In order to investigate the action of somatostatin-28 (SS-28) on the metabolic homeostasis of insulin-dependent diabetics, we compared its effects to those of somatostatin-14 (SS-14) in terms of insulin sparing, changes in dextrose demands, glucose fluctuations and behavior of growth hormone and glucagon secretion. Eight insulin-dependent subjects were connected to Artificial Endocrine Pancreas (Biostator) for 84 hours during which they received intravenous infusions of either SS-14, SS-28 or isotonic saline in a randomized order, after a steady state of metabolism had been achieved. Five of the patients received SS-28 100 micrograms/h and SS-14 250 micrograms/h for 10 hours and three of them SS-28, 50 micrograms/h and SS-14 250 micrograms/h for 12 hours. Identical doses of both peptides were administered as bolus infusions prior to the continuous ones. Under SS-28 100 micrograms/h and SS-14 250 micrograms/h patients required 13.5 +/- 2.3 and 14.5 +/- 1.9 U of insulin respectively vs 40 +/- 5.6 U under isotonic saline infusion (mean +/- SEM, P less than 0.005 and P less than 0.01). At the same period the apparatus delivered 15 times more dextrose under SS-28 and 20 times more under SS-14. The magnitude of glucose fluctuations diminished from 64.6 +/- 2.47 mg% without to 41.4 +/- 2 mg% under SS-14 (P less than 0.01) and 46 +/- 3.8 mg% under SS-28 (P less than 0.02). Similar changes were observed in the remaining three patients who received SS-28 in the dose of 50 micrograms/h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The antidiabetic action of somatostatin-28 as assessed by the artificial endocrine pancreas: greater potency than somatostatin-14. 289 70

Previous studies with heterogeneous populations of pancreatic cells have provided evidence for the presence of somatostatin (SRIF) receptors in cytosol and secretion vesicles, as well as the plasma membrane. To examine the distribution of SRIF receptors between soluble and membrane fractions in a homogeneous pancreatic islet cell population, we have used the clonal RINm5F insulinoma cell line. These cells contain specific, high affinity binding sites for [125I-Try11]SRIF on the cell surface, and occupancy of these sites by SRIF and SRIF analogs correlates with inhibition of insulin secretion. Stable, steady state binding was achieved using both intact cells and membranes by performing binding incubations with [25I-Tyr11]SRIF at 22 C. Half-maximal inhibition of [125I-Tyr11]SRIF binding occurred with 0.21 +/- 0.11 nM SRIF in membranes and 0.35 +/- 0.30 nM SRIF in cells. In contrast, the binding of [125I-Tyr11]SRIF to cytosolic macromolecules was not reduced by concentrations of SRIF as high as 100 nM, demonstrating that this binding was of much lower affinity. RINm5F membranes were further purified using a Percoll gradient to prepare a microsomal fraction, which was enriched in adenylate cyclase activity, and a secretory granule fraction, which was enriched in insulin. [125I-Tyr11]SRIF binding to the microsomal fraction (3.8 +/- 0.3 fmol/mg) was 3 times higher than to secretion granules (1.2 +/- 0.2 fmol/mg). Thus, high affinity SRIF binding sites were most abundant in microsomal membranes and were low or undetectable in secretory granules and cytosol. To determine whether translocation of SRIF receptors to the plasma membrane accompanied insulin secretion, we examined the effects of various insulin secretagogues on [125I-Tyr11]SRIF binding to intact cells. Leucine (20 mM), glyceraldehyde (15 mM), forskolin (1 microM), and glucagon (1 microM) stimulated insulin release 1.5- to 4.0-fold in different experiments. However, these secretagogues did not increase [125I-Tyr11]SRIF binding. In summary, our results indicate that high affinity SRIF receptors in RINm5F cells are located primarily on the plasma membrane and that the concentration of SRIF receptors at the cell surface is independent of the secretory activity of the cells.
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PMID:Distribution of somatostatin receptors in RINm5F insulinoma cells. 289 29

Isolated hepatocyte studies demonstrated that leucine can be a precursor of ketone bodies. In this study we examine the relative contribution of leucine to hepatic ketogenesis in vivo. Three groups of conscious dogs with long-term indwelling catheters in the femoral artery, hepatic vein, and portal vein were studied. Group I (n = 3) animals were fasted overnight for 24 hours, and those in groups II and III (n = 4, each) were fasted for 62 to 68 hours (designated 3-day fast). Groups I and III received intravenous saline solution (0.9%) and served as controls. In group II selective acute insulin deficiency (SAID) was induced by a peripheral intravenous somatostatin (SRIF) infusion and intraportal glucagon (0.55 ng/body weight/min). Net hepatic production (NHP) of ketone bodies (kb) and leucine (leu) was measured by the arteriovenous difference technique. Hepatic conversion of leucine to ketone bodies was measured by continuous infusion of L-U-[14C]-leucine and by determination of the appearance of [14C]-ketone bodies across the liver. In the group fasted overnight NHPleu was 0.02 +/- 0.01 mumol/kg/min, a value not different from zero. NHPkb was 3.1 +/- 0.1 mumol/kg/min and hepatic conversion of leucine to ketone bodies accounted for 3.5% of NHPkb. Insulin deficiency after 3 day's fasting resulted in a near 70% increase in NHPleu (from basal values of 0.31 +/- 0.1 mumol/kg/min to 0.52 +/- 0.06 mumol/kg/min during SAID, p less than 0.01). NHPkb increased from 11.0 +/- 1.0 to 15.5 mumol/kg/min (p less than 0.05). The rate of leucine conversion to ketone bodies (L-C) increased from 1.1 +/- 0.25 to 2.4 +/- 0.3 mumol/kg/min (p less than 0.01) with SAID. We conclude that as the dog progresses to fasting, the contribution of leucine carbon to hepatic production of ketone bodies increases from 3.5% to 10% (p less than 0.01), and this value increases to 15% (p less than 0.01 versus groups I and II) after SAID. Furthermore, the amount of leucine carbon taken up by the liver was not sufficient to account for all [14C]-labeled leucine to ketone bodies. The data suggest that the leucine carbon converted to ketone bodies must have been derived from intrahepatic protein sources of possibly from the keto acids of leucine, which are derived by the breakdown of leucine at distant sites, such as skeletal muscle or adipose tissue.
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PMID:The role of leucine in hepatic ketogenesis. 289 77

Invariant somatostatin-14 (SST-14) and somatostatin-25 (SST-25), isolated from coho salmon pancreas (Plisetskaya et al., 1986a) are likely coded by two distinct somatostatin genes. The present study was undertaken to investigate whether these genes are expressed in the same or in different cell types in the pancreatic islets and in the brain of two salmonids: rainbow trout and coho salmon. Antibodies generated against SST-14, mammalian (m) SST-28(1-14), salmon (s) SST-25, salmon insulin, and salmon glucagon were used as immunocytochemical probes. Two distinct cell types containing SSTs were revealed in the pancreas of both salmonid species: one cell type immunoreactive to both SST-14 and mSST-28(1-14) and the other cell type immunoreactive only to sSST-25. The SST-14/mSST-28(1-14)-positive cells were limited to the more central parts of the islets, in apposition to the insulin-positive cells: sSST-25-positive cells were located more peripherally and were associated topographically with the glucagon-positive cells. In contrast to the pancreas, neurons in the neurohypophysis and hypothalamus of the rainbow trout and coho salmon contained only SST-14-like and mSST-28(1-14)-like immunoreactivities, while immunoreactivity to sSST-25 was completely absent. These results suggest that differentiation in the pancreas and brain of salmonid fishes results in cell types in which SST genes are separately expressed. The close topographical association of sSST-25 with glucagon cells, and of SST-14 with insulin cells, in the pancreatic islets implies yet unknown functional regulatory relationships that require detailed study.
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PMID:Different cellular distributions of two somatostatins in brain and pancreas of salmonids, and their associations with insulin- and glucagon-secreting cells. 289 14

The selective binding of somatostatin-28 (SS-28) to beta cells of hamster insulinoma was characterized using HPLC-purified 125I-[Leu8,D-Trp22,Tyr25]SS-28 or 125I-SS-28. A single class of high-affinity sites (Kd = 53 +/- 5 pM) was observed with a binding capacity of 2.85 pmol/mg membrane protein. A large number of relatively low-affinity sites was found also. The order of potency of different peptides to inhibit 125I-SS-28 binding is SS-28 greater than SS-14 greater than SMS-201-995 and the respective half-maximal inhibitory doses are 0.16 nM, 10 nM and 1000 nM. CCK8 and other active pancreatic peptides (glucagon, insulin, gastric inhibitory peptide, vasoactive intestinal peptide, oxyntomodulin) do not inhibit the SS-28 receptor binding. 125I-SS-28-labeled beta membranes were successfully cross-linked using either the cleavable cross-linker dithiobis(succinimidylpropionate) (1 mM) alone or with a heterobifunctional agent, N-hydroxysuccinimidyl-4-azidobenzoate (HSAB). In both cases five molecular components were revealed, after polyacrylamide gel electrophoresis of the membrane proteins and autoradiography, with the following molecular mass: 196-kDa, 132 kDa, 69 kDa, 45 kDa and 28 kDa. The labeling of 196-kDa, 132-kDa and 45-kDa species was specific in that they could be inhibited by unlabeled SS-28. The major labeled species corresponds to the 132-kDa band and no change in the mobility of this HSAB covalently bound SS-28 receptor was found after addition of dithiothreitol, suggesting that this specific receptor does not contain interchain disulphide bonds. The molecular mass of SS-28 receptors differs markedly from that of guinea-pig pancreatic acinar membranes, where a single 93-kDa protein is identified as a 125I-SS-28 receptor site in comparative experiments. Both the binding kinetics and structural differences sustain the selective action of SS-28 in the endocrine pancreas.
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PMID:Characterization of covalently cross-linked somatostatin receptors in hamster beta cell insulinoma. 289 92

The aim of this study was to evaluate the contribution of gluconeogenesis from amino acids in the development of fasting and absorptive hyperammonemia in cirrhosis. Somatostatin (SRIF), which is known to inhibit the hepatic disposal of gluconeogenic amino acids, was administered in a continuous infusion (500 micrograms/h) for 90 min before and 5 h after a protein meal (240 g of meat) in 11 overnight fasting patients. Plasma glucagon, insulin, gluconeogenic amino acids (GAA: alanine, serine, glycine, and threonine) and ammonia (NH3) were evaluated before the infusion, immediately before, and at 1, 3, and 5 h after the meal. As control study, the same protocol was randomly repeated in a different day with saline infusion. During the latter, a direct correlation was found between fasting glucagon and ammonia (r = 0.68; p less than 0.05). Fasting glucagon, insulin, and NH3 did not change, whereas alanine (p less than 0.05) and the GAA sum decreased (p less than 0.01). When SRIF was infused, fasting glucagon (p less than 0.05), insulin (p less than 0.05), and NH3 (p less than 0.05) decreased. Alanine did not change, and GAA sum increased (p less than 0.02). No correlations were found by plotting changes in glucagon or GAA sum and NH3. After the meal, SRIF infusion abolished the plasma response of glucagon and markedly reduced that of insulin, so that their area under the curve (AUC0-5) were reduced (p less than 0.005, for both), with respect to control study. Moreover, the AUC0-5 of alanine (p less than 0.005) and GAA sum (p less than 0.005) were increased, suggesting a reduced disposal of these compounds. In spite of this, the meal-induced early increase and the AUC0-5 of plasma NH3 observed during SRIF and saline infusion did not differ. Our results do not confirm the importance of gluconeogenesis from alpha-amino-nitrogens in determining the fasting ammonemia of cirrhosis, and suggest that this metabolic pathway does not significantly influence the protein meal-induced exacerbation of plasma ammonia.
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PMID:Role of gluconeogenesis from amino acids in determining fasting and absorptive levels of plasma ammonia in cirrhosis. 289 85

We examined the contribution of glucose, independently of insulin, on fetal glucose kinetics in the sheep by infusing somatostatin (SRIF), followed by SRIF plus glucose (protocol A) or reversing the initial infusion sequence (protocol B). In protocol A (n = 8), infusion of SRIF at 200 micrograms/h decreased plasma insulin (IRI) and blood glucose (G) by 2.8 +/- 1.0 microU/ml and 1.34 +/- 0.2 mg/dl from their respective basal concentrations of 6.8 +/- 1.4 microU/ml and 16.47 +/- 0.91 mg/dl (P less than 0.05; P less than 0.005). There were no significant changes in plasma glucagon (IRG) or the rates of umbilical G uptake or of G utilization, but G turnover decreased by 1.77 +/- 0.34 mg.kg-1.min-1 (P less than 0.005). Addition of G at a rate of 5.6 +/- 0.8 mg.kg-1.min-1 had no effect on IRI and IRG. Total G uptake (G infusion rate plus umbilical G uptake) increased from 6.37 +/- 0.77 to 10.25 +/- 1.0 mg.kg-1.min-1 (P less than 0.01), despite suppression of umbilical G uptake by 33%. Fetal G reached a new steady state of 23.08 +/- 1.37 mg/dl, and G turnover increased by 4.81 +/- 0.96 mg.kg-1.min-1 from its SRIF-induced nadir (P less than 0.005). Since G concentration was maintained at steady state, the rate of G utilization was equivalent to the rate of total G uptake, an increase of 60% from basal despite suppressed IRI.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of somatostatin and glucose infusion on glucose kinetics in fetal sheep. 289 94

The effect of plasma amino acid and hormone (insulin, glucagon, and growth hormone) levels on renal hemodynamics was studied in 18 healthy subjects. The following four protocols were employed: study 1, a balanced amino acid solution was infused for 3 h to increase plasma amino acid concentrations two to three times base line; study 2, the same amino acid solution was infused with somatostatin (SRIF) and infusions of insulin, glucagon, and growth hormone were concomitantly administered to replace the time sequence of increase in peripheral concentrations of these hormones as observed during study 1; study 3, the same amino acid infusion was administered with SRIF plus infusions of insulin, glucagon, and growth hormone to maintain plasma hormone concentrations constant at the basal level; study 4, SRIF was infused with insulin, glucagon, and growth hormone to reproduce the time sequence of increase of these hormones as observed in study 1; amino acids were not infused in this study. During study 1, glomerular filtration rate (GFR) and renal plasma flow (RPF) rose by 19 and 21%, respectively. During study 2 both the time sequence of and magnitude of rise in GFR and in RPF were similar to the changes observed during study 1. In studies 3 and 4 neither RPF nor GFR changed significantly from base line. These results indicate that 1) hyperaminoacidemia stimulates insulin/glucagon/growth hormone secretion and causes a modest rise in GFR and RPF; and 2) if hyperaminoacidemia is created while maintaining basal hormone levels constant or if plasma insulin/glucagon/growth hormone levels are increased while maintaining the plasma amino acid concentration at basal levels, neither RPF nor GFR rise.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of plasma amino acid and hormone levels on renal hemodynamics in humans. 290 Dec 29

Peptides derived from prosomatostatins I and II and from two distinct proglucagons have been isolated from the pancreas of a teleost fish, the European eel (Anguilla anguilla). The product of prosomatostatin I processing, somatostatin-14, is identical to mammalian somatostatin-14. A 25-amino-acid-residue peptide (Ser-Val-Asp-Asn-Gln5-Gln-Gly-Arg-Glu-Arg10-Lys-Ala-Gly-Cys- Lys15-Asn-Phe-Tyr- Trp-Lys20-Gly-Pro-Thr-Ser-Cys25) is derived from prosomatostatin II. Compared with the corresponding peptides from other teleost fish, the eel somatostatin-25 contains the unusual substitution Pro for Phe at position 22. This peptide was also isolated in a form containing a hydroxylsyl residue at position 20. A 29-amino-acid-residue eel glucagon contains four substitutions relative to human glucagon Asn for Ser8, Glu for Asp15, Thr for Ser16, and Ser for Thr29). In common with mammalian and avian glucagons but unlike most other fish glucagons, the eel peptide possesses a glutamine residue at position 3. A peptide derived from a second proglucagon comprises 36 amino acid residues. A 7-residue C-terminal extension to the glucagon sequence shows structural similarity to the corresponding extension in ratfish (Hydrolagus colliei) glucagon and mammalian oxyntomodulin.
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PMID:Somatostatin-related and glucagon-related peptides with unusual structural features from the European eel (Anguilla anguilla). 290 91


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