Interaction of gastric inhibitory polypeptide and arginine with glucose in the perfused pancreas of rats treated with triiodothyronine

1982 ◽  
Vol 60 (3) ◽  
pp. 297-301 ◽  
Author(s):  
Michael K. Mueller ◽  
Raymond A. Pederson ◽  
John C. Brown
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Chronic Treatment ◽  
Gastric Inhibitory Polypeptide ◽  
Second Phase ◽  
Perfused Pancreas ◽  
Isolated Pancreas ◽  
Insulinotropic Effect

Chronic treatment of rats with triiodothyronine (T3) resulted in suppression of insulin release from the isolated pancreas when perfused with 8.6 mM glucose. This inhibition could be partially overcome by 16 mM glucose but the insulin release was still significantly reduced. Arginine and gastric inhibitory polypeptide (GIP) induced an insulinotropic action in both control and T3-treated preparations. This was achieved in the latter, in the absence of a second phase of insulin secretion to glucose. The insulinotropic effect of both arginine and GIP was abolished by mannoheptulose in both control and T3-treated animals.

Different dynamics of insulin secretion in the perfused pancreas of mouse and rat

1980 ◽  
Vol 93 (1) ◽  
pp. 54-60 ◽  
Author(s):  
Ove Berglund
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Glucose Concentration ◽  
Inbred Mice ◽  
Second Phase ◽  
Perfused Pancreas ◽  
First Response ◽  
Dynamics Of Insulin Secretion ◽  
Rats And Mice ◽  
Secretory Pattern

Abstract. The dynamics of insulin release were studied in the perfused pancreas of rats and mice. Perfusion of the rat pancreas with 20 mm D-glucose resulted in the classical biphasic release of insulin with a rising second phase. However, in normal C57BL/KsJ-mice and noninbred mice, whether fed or starved, the second phase was nearly constant. The secretory dymanics of KsJ-mice were essentially the same, whether the glucose concentration was 30 or 20 mm, whether the medium contained 2.56 or 8 mm Ca2+, and whether or not the medium was supplemented with 5 mm pyruvate, 5 mm glutamate, and 5 mm fumarate. Insulin secretion in these mice was almost totally inhibited by omission of Ca2+, and was markedly enhanced by 3-isobutyl-1-methylxanthine. Insulin release during the constant phase was reversed by lowering the glucose concentration. A second rise of glucose from 3 to 20 mm produced a secretory pattern very similar to the first response. These studies indicate that the dynamics of insulin secretion are somewhat different in rats and mice. Since similar results were obtained with C57BL/KsJ-mice and non-inbred mice, the liability of KsJ-mice to develop β-cell failure when stressed by the mutated db gene is not related to the constancy of the second insulin secretory phase.

Differences in insulin secretion between the rat and mouse: role of cAMP

1995 ◽  
Vol 132 (3) ◽  
pp. 370-376 ◽  
Author(s):  
Yan Hui Ma ◽  
Jian Wang ◽  
Gail G Rodd ◽  
Janice L Bolaffi ◽  
Gerold M Grodsky
Keyword(s):  
Body Weight ◽  
Insulin Secretion ◽  
Beta Cells ◽  
Insulin Release ◽  
Second Phase ◽  
Perfused Pancreas ◽  
Rat Pancreas ◽  
Mouse Islets ◽  
Camp Levels

Ma YH, Wang J, Rodd GG, Bolaffi JL, Grodsky GM. Differences in insulin secretion between the rat and mouse: role of cAMP. Eur J Endocrinol 1995;132:370–6. ISSN 0804–4643 Although information regarding insulin secretion usually is considered equivalent when generated in the mouse or the rat, it is established that the kinetics of insulin secretion from mouse and rat pancreatic beta cells differ. The mechanisms underlining these differences are not understood. The in vitro perfused pancreas and isolated islets of the mouse or rat were employed in this study to investigate the role of cyclic adenosine monophosphate (cAMP), a major positive modulator of betacell function, as one differentiating signal for the uniquely different insulin release from the beta cells of these commonly used rodents. Glucose-stimulated first-phase insulin release from the perfused pancreas of the rat was higher than the mouse when calculated per gram of pancreas or as fractional secretion, but this phase was identical in the two species when results were adjusted for total body weight. Whether related to insulin content, pancreatic weight or body weight, the rat pancreas responded to glucose with a progressively increasing second-phase insulin release compared to the mouse pancreas, which secreted a flat second-phase of lesser magnitude. Isolated islets from rat and mouse were comparable in insulin content whereas the basal cAMP level of mouse islets was less than half that of the rat. At submaximal stimulation with glucose or glucose + IBMX or forskolin, mouse islets exhibited lower cAMP levels to a given stimulus than the rat. In rat islets cAMP levels increased to approximately 1000 fmol per islet, although insulin secretion maximized by 100–150 fmol. Insulin release at the same 100–150fmol cAMP per mouse islet was one-third that of the rat and secretion had not maximized in mouse islets at 800 fmol. Despite their similar insulin contents, mouse islets consistently secreted less insulin for a given level of cAMP per islet than the rat. The lower capacity of mouse islets to achieve comparable cAMP levels was not the result of increased catabolic rate because the "half-time" disappearance of islet cAMP after a stimulus was similar (~1 min) for both species. It is concluded that, compared to the mouse, beta cells of the rat pancreas elicit a more pronounced secondphase insulin secretion that is due, at least in part, to a greater production of, and sensitivity to, cAMP. Gerold M Grodsky, Metabolic Research Unit, University of California, H5W 1157, Box 0540, 3rd and Parnassus Avenue, San Francisco, CA 94143, USA

Effect of galanin on glucose-, arginine-, or potassium-stimulated insulin release

1989 ◽  
Vol 256 (5) ◽  
pp. E619-E623
Author(s):  
T. Yoshimura ◽  
J. Ishizuka ◽  
G. H. Greeley ◽  
J. C. Thompson
Keyword(s):  
Insulin Release ◽  
High Glucose ◽  
Second Phase ◽  
Dependent Manner ◽  
Perfused Pancreas ◽  
Isolated Perfused Pancreas ◽  
Second Phases ◽  
High Concentrations ◽  
Dose Dependent ◽  
Stimulation Of

We have examined the effect of galanin infusion on glucose-stimulated release of insulin from the isolated perfused pancreas of the rat to better characterize the effect of galanin on the first and second phases of insulin release. The effects of galanin on insulin release stimulated by L-arginine or high concentrations of potassium were also examined. When perfusion of galanin was started 4 min before the start of perfusion of high glucose (16.7 mM), galanin (10(-8)-10(-11) M) inhibited both the first and second phases of insulin release in a dose-dependent manner. When perfusion of galanin (10(-8) or 10(-9) M) was started simultaneously with high glucose (16.7 mM), only the second phase of insulin release was suppressed (P less than 0.05). Galanin (10(-9) M) failed to inhibit insulin release stimulated by L-arginine (10 and 5 mM) or potassium (25 and 20 mM). These findings suggest that the inhibitory action of galanin on glucose-stimulated insulin release is exerted on early intracellular events that occur during the stimulation of insulin release and that are common to both phases. Because galanin does not inhibit insulin release stimulated by L-arginine or potassium, galanin may inhibit glucose-stimulated closure of potassium channels.

scholarly journals Detrimental actions of metabolic syndrome risk factor, homocysteine, on pancreatic β-cell glucose metabolism and insulin secretion

2006 ◽  
Vol 189 (2) ◽  
pp. 301-310 ◽  
Author(s):  
S Patterson ◽  
P R Flatt ◽  
L Brennan ◽  
P Newsholme ◽  
N H McClenaghan
Keyword(s):  
Metabolic Syndrome ◽  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Insulin Release ◽  
Cell Function ◽  
Tca Cycle ◽  
Gastric Inhibitory Polypeptide ◽  
Β Cell ◽  
The Metabolic Syndrome ◽  
Cell Glucose

Elevated plasma homocysteine has been reported in individuals with diseases of the metabolic syndrome including vascular disease and insulin resistance. As homocysteine exerts detrimental effects on endothelial and neuronal cells, this study investigated effects of acute homocysteine exposure on β-cell function and insulin secretion using clonal BRIN-BD11 β-cells. Acute insulin release studies in the presence of various test reagents were performed using monolayers of BRIN-BD11 cells and samples assayed by insulin radioimmunoassay. Cellular glucose metabolism was assessed by nuclear magnetic resonance (NMR) analysis following 60-min exposure of BRIN-BD11 cell monolayers to glucose in either the absence or presence of homocysteine. Homocysteine dose-dependently inhibited insulin release at moderate and stimulatory glucose concentrations. This inhibitory effect was reversible at all but the highest concentration of homocysteine. 13C-glucose NMR demonstrated decreased labelling of glutamate from glucose at positions C2, C3 and C4, indicating that the tricarboxylic acid (TCA) cycle-dependent glucose metabolism was reduced in the presence of homocysteine. Homocysteine also dose-dependently inhibited insulinotropic responses to a range of glucose-dependent secretagogues including nutrients (alanine, arginine, 2-ketoisocaproate), hormones (glucagon-like peptide-1 (7–36)amide, gastric inhibitory polypeptide and cholecystokinin-8), neurotransmitter (carbachol), drug (tolbutamide) as well as a depolarising concentration of KCl or elevated Ca2+. Insulin secretion induced by activation of adenylate cyclase and protein kinase C pathways with forskolin and phorbol 12-myristate 13-acetate were also inhibited by homocysteine. These effects were not associated with any adverse action on cellular insulin content or cell viability, and there was no increase in apoptosis/necrosis following exposure to homocysteine. These data indicate that homocysteine impairs insulin secretion through alterations in β-cell glucose metabolism and generation of key stimulus-secretion coupling factors. The participation of homocysteine in possible β-cell demise merits further investigation.

Interleukin-1 potentiates glucose stimulated insulin release in the isolated perfused pancreas

1988 ◽  
Vol 117 (3) ◽  
pp. 302-306 ◽  
Author(s):  
Lise D. Wogensen ◽  
Thomas Mandrup-Poulsen ◽  
Helle Markholst ◽  
Jens Mølvig ◽  
Åke Lernmark ◽  
...  
Keyword(s):  
Insulin Release ◽  
Cell Function ◽  
Interleukin 1 ◽  
Systemic Circulation ◽  
Second Phase ◽  
Interleukin 1 Beta ◽  
Perfused Pancreas ◽  
Porcine Pancreas ◽  
Isolated Perfused Pancreas

Abstract. The acute effects of recombinant human interleukin-1 beta (rIL-1) on basal and glucose-stimulated insulin release were investigated in the isolated perfused pancreas. At a concentration of 20 μg/l rIL-1 had no effect on basal insulin release, but increased the total amount of insulin released during first and second phase insulin release in response to 20 mmol/l D-glucose in the rat pancreas (P < 0.05). In addition, 26 μg/l of rIL-1 potentiated insulin release in response to square wave infusions of stimulatory concentrations of glucose (11 mmol/l) in the porcine pancreas. We hypothesize that IL-1 in the systemic circulation may affect B cell function in vivo.

Differential effects of microtubule-altering agents on beta-cells during development

1983 ◽  
Vol 245 (4) ◽  
pp. E391-E400
Author(s):  
R. S. Hill ◽  
W. B. Rhoten
Keyword(s):  
Insulin Secretion ◽  
Beta Cells ◽  
Insulin Release ◽  
High Glucose ◽  
Deuterium Oxide ◽  
Inhibitory Effect ◽  
Secretory Response ◽  
Second Phase ◽  
Insulin Secretory Response

The effect of microtubule-altering agents on the insulin secretory response to glucose during the perinatal period was investigated with an in vitro perifusion system. Rat pancreatic mince from day 17 of gestation (D17G) to day 6 postnatally (D6PN) were perifused for 60 min in basal glucose followed by 45 min with high glucose (3.5 mg/ml) or with high glucose plus 10 mM arginine (D17G). The two phases of insulin secretion in response to high glucose developed in an age-dependent and asynchronous manner. The first phase matured between D17G and D18G, and maturation of the second phase occurred subsequently. Vinblastine (VB) (20 or 100 microM) had a differential effect on the insulin secretory response. VB did not inhibit stimulated insulin release at D17G. This absence of an inhibitory effect of VB at D17G could not be explained by the absence of polymerized tubulin because microtubules were present in the control beta-cells and, in addition, VB treatment resulted in the formation of paracrystalline deposits. Subsequently in development, and with isolated islets of the adult, VB inhibited stimulated insulin release. Heavy water (deuterium oxide, D2O) inhibited stimulated insulin secretion at D17G but blocked completely insulin release from the near-term beta-cell. The inhibition of insulin secretion by D2O was rapidly reversed when water replaced D2O in the perifusion media. The results indicate that the maturation of the second phase of insulin secretion coincides with the ability of the microtubule-altering agents to modify the insulin secretory response. One possible explanation for these findings is that at D17G the microtubules are not coupled physicochemically to other molecules or structures necessary for their role in insulin secretion to be expressed fully.

Lack of glucose-induced priming of insulin release in the perfused mouse pancreas

1987 ◽  
Vol 114 (2) ◽  
pp. 185-189 ◽  
Author(s):  
O. Berglund
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Mesenteric Artery ◽  
Insulin Response ◽  
Second Phase ◽  
Mouse Pancreas ◽  
Rat Pancreas ◽  
Continuous Stimulation ◽  
Insulin Responses ◽  
Biphasic Release

ABSTRACT Perfusion of the mouse or rat pancreas with 20 mmol d-glucose/l caused a biphasic release of insulin. The second phase was nearly constant in the mouse but rose in the rat. Repeated pulses of 8, 20 or 30 mmol d-glucose/l did not potentiate subsequent insulin responses in the mouse, whereas repeated pulses of 20 mmol/l did in the rat. When 20 mmol d-glucose/l was introduced through the mesenteric artery or aorta of the mouse, the pattern of insulin release was the same as when it was introduced through the coeliac artery. Thus, insulin secretion in mice differs from that in rats both in not showing an increasing second phase in response to continuous stimulation with glucose and also in not showing successive enhancement in the insulin response to repeated pulses of glucose. J. Endocr. (1987) 114, 185–189

scholarly journals The Effect of Age and Glycemic Level on the Response of theβ -Cell to Glucose-Dependent Insulinotropic Polypeptide and Peripheral Tissue Sensitivity to Endogenously Released Insulin1

1998 ◽  
Vol 83 (8) ◽  
pp. 2925-2932 ◽  
Author(s):  
Graydon S. Meneilly ◽  
Alice S. Ryan ◽  
Kenneth L. Minaker ◽  
Dariush Elahi
Keyword(s):  
Insulin Release ◽  
Insulin Response ◽  
Normal Aging ◽  
Second Phase ◽  
Β Cell ◽  
Cell Sensitivity ◽  
Age Related ◽  
Basal Plasma ◽  
Age Range ◽  
Insulinotropic Effect

abstract Normal aging is characterized by a progressive impairment in glucose tolerance. An important mechanism underlying the glucose intolerance of aging is an impairment in glucose-induced insulin release. These studies were conducted to determine whether the age-related impairment in insulin release was caused by a decreased β-cell sensitivity to glucose-dependent insulinotropic polypeptide (GIP). Thirty-one Caucasian men were divided into four groups: two young groups (age range: 19–26 yr, n = 15) and two old groups (age range: 67–79 yr, n = 16). Each volunteer participated in three studies (n= 93 clamps). Hyperglycemic clamps were conducted at two doses [basal plasma glucose (G) + 5.4 mmol/L and G + 12.8 mmol/L] for 120 min. In the initial hyperglycemic clamp, only glucose was infused. In subsequent studies, GIP was infused at a final rate of 2 or 4 pmol/kg−1·min−1 from 60–120 min. Basal plasma insulin and GIP levels were similar in the young (41 ± 6 and 51 ± 6 pmol/L) and the old subjects (42 ± 6 and 66± 12 pmol/L) in all studies. First- and second-phase insulin responses were similar during the control study and during the first 60 min of each GIP infusion study in both groups. The 90–120 min GIP values were similar between groups and between hyperglycemic plateaus during the 2 and 4 pmol/kg−1·min−1 GIP infusion (young: 342 ± 28 and 601 ± 44 pmol/L, old: 387 ± 45 and 568 ± 49 pmol/L). In response to the GIP infusions, significant increases in insulin occurred in young and old at both glucose levels (P &lt; 0.01). The potentiation of the insulin response caused by GIP was greater in the young subjects than in the old, in the G + 5.4 mmol/L studies (P &lt; 0.05). However, the insulin response to GIP was similar in both young and old during the G + 12.8 mmol/L clamps. The insulinotropic effect of the incretin was higher in the young and in the old, in the G + 12.8 mmol clamps, than in the G + 5.4 mmol/L clamps. We conclude that normal aging is characterized by a decreased β-cell sensitivity to GIP during modest hyperglycemia, which may explain, in part, the age-related impairment in glucose-induced insulin release. We also find that the insulinotropic effect of GIP is increased with increasing levels of hyperglycemia.

scholarly journals Regulation of insulin secretion by energy metabolism in pancreatic B-cell mitochondria. Studies with a non-metabolizable leucine analogue

1984 ◽  
Vol 219 (1) ◽  
pp. 189-196 ◽  
Author(s):  
U Panten ◽  
S Zielmann ◽  
J Langer ◽  
B J Zünkler ◽  
S Lenzen
Keyword(s):  
Insulin Secretion ◽  
Oxidative Phosphorylation ◽  
B Cell ◽  
Insulin Release ◽  
Prolonged Exposure ◽  
Mitochondrial Fraction ◽  
Second Phase ◽  
O2 Uptake ◽  
Hydrogen Supply ◽  
Kinetics Of

In mouse pancreatic islets the kinetics of insulin secretion and O2 uptake in response to the non-metabolizable leucine analogue (+/-)-BCH (2-endo- aminonorbornane −2-carboxylic acid) were compared. In addition, the fuel-mobilizing effect of (+/-)-BCH was studied with a mitochondrial fraction from islets. (1) Within 2 min 20 mM-(+/-)-BCH markedly enhanced insulin release or O2 consumption by islets respiring in the absence of exogenous fuels. During prolonged exposure to 20 mM-(+/-)-BCH secretion declined more rapidly than O2 uptake. (2) L-Glutamine (10 mM) prevented the decrease of both insulin release and O2 uptake of islets exposed to 20mM-(+/-)-BCH. During the second phase of insulin release in response to 20 mM-(+/-)-BCH + 10 mM-L-glutamine, kinetics of secretion and respiration correlated closely. (3) Initial peaks were consistently seen in the (+/-)-BCH-induced secretory profiles, but never in the respiratory profiles. (4) In contrast with L-glycerol 3-phosphate, L-malate or pyruvate, L-glutamine or L-glutamate maintained low rates of oxidative phosphorylation in B-cell mitochondria. The effects of L-glutamine or L-glutamate were potentiated severalfold by (+/-)-BCH. (5) The effects of other branched-chain amino acids on oxidative phosphorylation resembled their effects on insulin release, redox state of nicotinamide nucleotides and glutamate dehydrogenase activity. (6) The results support the view that (+/-)-BCH stimulates insulin secretion via a primary enhancement of hydrogen supply to the respiratory chain of B-cell mitochondria.

Nutritional recovery from a low-protein diet during pregnancy does not restore the kinetics of insulin secretion and Ca2+ or alterations in the cAMP/PKA and PLC/PKC pathways in islets from adult rats

2018 ◽  
Vol 43 (12) ◽  
pp. 1257-1267
Author(s):  
Leonardo Marin ◽  
Hellen Barbosa Faria Silva ◽  
Gabriela Damin ◽  
Letícia Martins Ignacio-Souza ◽  
Sílvia Regina de Lima Reis ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Insulin Release ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Second Phase ◽  
Adult Rats ◽  
Low Protein ◽  
Nutritional Recovery ◽  
Kinetics Of

We investigated the insulin release induced by glucose, the Ca2+ oscillatory pattern, and the cyclic AMP (cAMP)/protein kinase A (PKA) and phospholipase C (PLC)/protein kinase C (PKC) pathways in islets from adult rats that were reared under diets with 17% protein (C) or 6% protein (LP) during gestation, suckling, and after weaning and in rats receiving diets with 6% protein during gestation and 17% protein after birth (R). First-phase glucose-induced insulin secretion was reduced in LP and R islets, and the second phase was partially restored in the R group. Glucose stimulation did not modify intracellular Ca2+ concentration, but it reduced the Ca2+ oscillatory frequency in the R group compared with the C group. Intracellular cAMP concentration was higher and PKA-Cα expression was lower in the R and LP groups compared with the C group. The PKCα content in islets from R rats was lower than that in C and LP rats. Thus, nutritional recovery from a low-protein diet during fetal life did not repair the kinetics of insulin release, impaired Ca2+ handling, and altered the cAMP/PKA and PLC/PKC pathways.

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