L-leucine or its keto acid potentiate but do not initiate insulin release in chicken

1989 ◽  
Vol 257 (1) ◽  
pp. E15-E19 ◽  
Author(s):  
N. Rideau ◽  
J. Simon
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Glucose Concentration ◽  
Progressive Increase ◽  
The Other ◽  
Keto Acid ◽  
Biphasic Insulin ◽  
Low Glucose ◽  
Biphasic Insulin Release ◽  
Chicken Pancreas

In the isolated perfused chicken pancreas, 20 and 40 mM L-leucine or 10–40 mM alpha-ketoisocaproic acid (alpha-KIC) did not initiate insulin release. In the presence of 14 mM glucose (a noninsulinotropic concentration), 20 mM L-leucine and 10 mM alpha-KIC evoked a slight biphasic insulin release. The response to 20 mM L-leucine was further increased when 14 mM glucose was combined with 10 mM L-glutamine (10 mM glutamine alone did not induce insulin release and did not potentiate the response to 10 mM L-leucine). At 1 mM, 8-bromo-adenosine 3',5'-cyclic monophosphate (8-BrcAMP) alone caused a slight and progressive increase in insulin secretion but did not sensitize the pancreas to either 20 mM L-leucine or 10 mM alpha-KIC, whereas it facilitated a marked insulin release in response to 14 mM glucose. On the other hand, 10–40 mM K+ or 20 mM L-arginine induced a rapid monophasic insulin output. In conclusion, L-leucine or alpha-KIC, which do not initiate insulin release alone and are not potentiated by 8-BrcAMP, may not be regarded as primary insulinotropic agents in the chicken. This result, together with the previously documented resistance of the chicken pancreas to glucose alone or to D-glyceraldehyde, strongly suggests that the mechanisms initiating insulin secretion are different in chickens and mammals, whereas potentiating mechanisms (low glucose concentration, arginine, acetylcholine, and cAMP) and membrane depolarization events (K+ and arginine) are present in both chickens and mammals.

Effects of Caffeine and Acetylcholine on Glucose-Stimulated Insulin Release from Islet Transplants in Mice

1997 ◽  
Vol 6 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Chun-Liang Shi
Keyword(s):  
Insulin Secretion ◽  
Intracellular Calcium ◽  
Insulin Release ◽  
Cholinergic Receptors ◽  
Mouse Islet ◽  
Kidney Capsule ◽  
Biphasic Insulin ◽  
Biphasic Insulin Release ◽  
Islet Transplants

In mouse islet grafts under the kidney capsule, the potentiating responsiveness to acetylcholine was markedly attenuated after a few weeks. The question arose as to whether transplanted islets show an decreased responsiveness to potentiators in general. The effect of caffeine on glucose-induced insulin secretion was, therefore, examined. Intrastrain transplantation was performed in NMRI and BALB/c mice, and islet grafts were removed and perifused in vitro after 3 and 12 wk. In grafts from both NMRI and BALB/c mice, 16.7 mmol/L glucose induced a biphasic insulin release. When 1 or 5 mmol/L caffeine was included in the perifusion medium, there was a marked potentiation of the glucose-induced insulin release that was at least as responsiveness as fresh untransplanted islets. In the absence of caffeine, 3-wk-old BALB/c grafts reacted less strongly to acetylcholine than did untransplanted islets. The addition of 1 mmol/L caffeine did not enhance the potentiating effect of acetylcholine, whether in untransplanted or transplanted islets. Rather, the interaction between caffeine and acetylcholine appeared negative. We concluded that the glucose-induced insulin secretion exhibits a diminished potentiatory responsiveness to acetylcholine but not to caffeine. The displacement and denervation of transplanted islets is likely to affect either the cholinergic receptors or their mediated influence on intracellular calcium. Copyright © 1997 Elsevier Science Inc.

Regulation of avian insulin secretion by isolated perfused chicken pancreas

1976 ◽  
Vol 231 (6) ◽  
pp. 1830-1839 ◽  
Author(s):  
DL King ◽  
RL Hazelwood
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Insulin Release ◽  
Transient Response ◽  
Glucose Concentration ◽  
Insulin Response ◽  
Secretory Rate ◽  
Insulin Responses ◽  
Chicken Pancreas

Chicken insulin secretory responses to glucose, glucagon, tolbutamide, and lack of Mg2+ were measured using isolated perfused in situ chicken pancreata. Although elevating perfusate glucose concentration from 100 to 250 mg/100 ml failed to increase insulin release, 500 mg glucose/100 ml provoked a transient 5-min insulin response. Additionally, 700 mg glucose/100 ml resulted in both a transient response and subsequent elevation in secretory rate that continued throughout the following 50-min stimulatory period. Glucagon (500 microgram/ml) and omission of perfusate Mg2+ potentiated glucose-stimulated insulin output by 6 and 25%, respectively. A faster release of insulin (less than 1 min) occurred during tolbutamide infusion (0.13 mg/ml) than with either 500 or 700 mg glucose per 100 ml (2-3 min); however, secretory rates declined to near basal levels within 5 min. Mammalian-like insulin responses to glucose, glucagon, Mg2+ lack, and tolbutamide suggest similarities between avian and mammalian beta-cell insulin secretory mechanisms. Nevertheless, the relatively high chicken insulin release threshold and low insulin output to glucose indicate that chicken pancreata are relatively glucose insensitive.

scholarly journals Reducing Glucokinase Activity Restores Endogenous Pulsatility and Enhances Insulin Secretion in Islets From db/db Mice

Endocrinology ◽  
2018 ◽  
Vol 159 (11) ◽  
pp. 3747-3760 ◽  
Author(s):  
Ishrat Jahan ◽  
Kathryn L Corbin ◽  
Avery M Bogart ◽  
Nicholas B Whitticar ◽  
Christopher D Waters ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Opposite Effect ◽  
Glucose Sensing ◽  
Β Cell ◽  
Left Shift ◽  
Low Glucose ◽  
Mouse Islets ◽  
Secretion Rates

Abstract An early sign of islet failure in type 2 diabetes (T2D) is the loss of normal patterns of pulsatile insulin release. Disruptions in pulsatility are associated with a left shift in glucose sensing that can cause excessive insulin release in low glucose (relative hyperinsulinemia, a hallmark of early T2D) and β-cell exhaustion, leading to inadequate insulin release during hyperglycemia. Our hypothesis was that reducing excessive glucokinase activity in diabetic islets would improve their function. Isolated mouse islets were exposed to glucose and varying concentrations of the glucokinase inhibitor d-mannoheptulose (MH) to examine changes in intracellular calcium ([Ca2+]i) and insulin secretion. Acutely exposing islets from control CD-1 mice to MH in high glucose (20 mM) dose dependently reduced the size of [Ca2+]i oscillations detected by fura-2 acetoxymethyl. Glucokinase activation in low glucose (3 mM) had the opposite effect. We then treated islets from male and female db/db mice (age, 4 to 8 weeks) and heterozygous controls overnight with 0 to 10 mM MH to determine that 1 mM MH produced optimal oscillations. We then used 1 mM MH overnight to measure [Ca2+]i and insulin simultaneously in db/db islets. MH restored oscillations and increased insulin secretion. Insulin secretion rates correlated with MH-induced increases in amplitude of [Ca2+]i oscillations (R2 = 0.57, P < 0.01, n = 10) but not with mean [Ca2+]i levels in islets (R2 = 0.05, not significant). Our findings show that correcting glucose sensing can restore proper pulsatility to diabetic islets and improved pulsatility correlates with enhanced insulin secretion.

scholarly journals Defective calcium handling and insulin release in islets from diabetic Chinese hamsters

1979 ◽  
Vol 180 (1) ◽  
pp. 233-236 ◽  
Author(s):  
E G Siegel ◽  
C B Wollheim ◽  
G W Sharp ◽  
L Herberg ◽  
A E Renold
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Chinese Hamster ◽  
Calcium Handling ◽  
Biphasic Insulin ◽  
Chinese Hamsters ◽  
Diabetic Chinese Hamsters ◽  
Biphasic Insulin Release

In pancreatic islets from normal Chinese hamsters preloaded with 45Ca2+, glucose-induced biphasic insulin release was associated with increased 45Ca2+ efflux; islets from diabetic hamsters showed decreased insulin release and no increase in 45Ca2+ efflux. The lack of stimulated 45Ca2+ efflux persisted even when glucose-induced insulin release was potentiated by 3-isobutyl-1-methylxanthine. Since glucose-stimulated 45Ca2+ uptake by diabetic islets was not impaired, a defect in intracellular Ca2+ handling may be involved in the defective insulin release of the diabetic Chinese hamster.

A role for endogenous prostaglandin E in biphasic pattern of insulin release in humans

1983 ◽  
Vol 245 (6) ◽  
pp. E591-E597 ◽  
Author(s):  
D. Giugliano ◽  
P. Di Pinto ◽  
R. Torella ◽  
N. Frascolla ◽  
F. Saccomanno ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Insulin Response ◽  
Physiological Role ◽  
Prostaglandin E ◽  
Glucose Stimulation ◽  
Biphasic Pattern ◽  
Endogenous Prostaglandin ◽  
Lysine Acetylsalicylate ◽  
Biphasic Insulin Release

These studies were undertaken to evaluate in humans the possible physiological role of prostaglandins of the E series (PGE) in modulating insulin release and to assess whether endogenous PGE synthesis may account for the biphasic pattern of insulin secretion. We used a square-wave glucose stimulation previously determined to give maximal biphasic insulin release. Infusion of lysine acetylsalicylate to block the synthesis of endogenous PGE increased by twofold total insulin response to glucose and also converted insulin release to a multiphasic pattern. The infusion of exogenous PGE1 (0.2 microgram X kg-1 X min-1) or PGE2 (10 micrograms/min) in addition to lysine acetylsalicylate restored the typical biphasic pattern of insulin release and also decreased total insulin release to values similar to those of control studies. Infusion of either PGE1 or PGE2 in the absence of lysine acetylsalicylate reset insulin secretion to a lower level without altering the kinetics of release. On the basis of these results, it is hypothesized that endogenous PGE released in response to glucose stimulation exert an inhibiting effect on insulin release that becomes biphasic in appearance.

scholarly journals 1-Hour OGTT Plasma Glucose as a Marker of Progressive Deterioration of Insulin Secretion and Action in Pregnant Women

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Alessandra Ghio ◽  
Giuseppe Seghieri ◽  
Cristina Lencioni ◽  
Roberto Anichini ◽  
Alessandra Bertolotto ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Pregnant Women ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Insulin Action ◽  
Progressive Increase ◽  
Plasma Glucose Concentration ◽  
Linear Manner

Considering old GDM diagnostic criteria, alterations in insulin secretion and action are present in women with GDM as well as in women with one abnormal value (OAV) during OGTT. Our aim is to assess if changes in insulin action and secretion during pregnancy are related to 1-hour plasma glucose concentration during OGTT. We evaluated 3 h/100 g OGTT in 4,053 pregnant women, dividing our population on the basis of 20 mg/dL increment of plasma glucose concentration at 1 h OGTT generating 5 groups (<120 mg/dL,n=661; 120–139 mg/dL,n=710; 140–159 mg/dL,n=912; 160–179 mg/dL,n=885; and ≥180 mg/dL,n=996). We calculated incremental area under glucose (AUCgluc) and insulin curves (AUCins), indexes of insulin secretion (HOMA-B), and insulin sensitivity (HOMA-R), AUCins/AUCgluc. AUCglucand AUCinsprogressively increased according to 1-hour plasma glucose concentrations (bothP<0.0001for trend). HOMA-B progressively declined (P<0.001), and HOMA-R progressively increased across the five groups. AUCins/AUCglucdecreased in a linear manner across the 5 groups (P<0.001). Analysing the groups with 1-hour value <180 mg/dL, defects in insulin secretion (HOMA-B: −29.7%) and sensitivity (HOMA-R: +15%) indexes were still apparent (allP<0.001). Progressive increase in 1-hour OGTT is associated with deterioration of glucose tolerance and alterations in indexes of insulin action and secretion.

Effect of fatty acids on insulin release: role of chain length and degree of unsaturation

1994 ◽  
Vol 266 (4) ◽  
pp. E635-E639 ◽  
Author(s):  
E. C. Opara ◽  
M. Garfinkel ◽  
V. S. Hubbard ◽  
W. M. Burch ◽  
O. E. Akwari
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Fatty Acid ◽  
Insulin Release ◽  
Glucose Concentration ◽  
Basal Insulin ◽  
Degree Of Unsaturation ◽  
Structural Differences ◽  
Basal Insulin Secretion

The purpose of the present study was to examine the role played by structural differences among fatty acids in their effect on insulin secretion by isolated perifused murine islets. Insulin secretion measured by radioimmunoassay was assessed either as total insulin output (ng.6 islets-1.20 min-1) or as percent of basal insulin secretion. Raising the glucose concentration from a basal 5.5 to 27.7 mM caused an increase of insulin output from 6.69 +/- 1.59 to 19.92 +/- 4.99 ng.6 islets-1.20 min-1 (P < 0.05) in control (untreated) islets. However, after 20-min exposure of islets to 5 mM 16:0 or 18:2, the effect of 27.7 mM glucose was enhanced or diminished, respectively. Basal insulin output (100% basal) changed to 44 +/- 10% basal (P < 0.005) with the addition of 5 mM 4:0 but was not altered when 4:0 was replaced by 6:0. Insulin output increased modestly with 5 mM 8:0 but significantly (P < 0.05) with 10:0 until a maximal of 280 +/- 24% basal with 12:0 (P < 0.01), then fell to 110 +/- 18 and 93 +/- 15% basal (P < 0.05) with 14:0 and 16:0, respectively. The addition of 5 mM 18:0 inhibited insulin secretion to 30 +/- 10% of basal (P < 0.003), and this effect was not caused by fatty acid interference with insulin assay.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Development of the biphasic response to glucose in fetal and neonatal rat pancreas

1988 ◽  
Vol 254 (2) ◽  
pp. E167-E174 ◽  
Author(s):  
R. L. Hole ◽  
M. C. Pian-Smith ◽  
G. W. Sharp
Keyword(s):  
Beta Cell ◽  
Insulin Release ◽  
Neonatal Rat ◽  
Biphasic Response ◽  
Rat Pancreas ◽  
K Channels ◽  
Fetal Pancreas ◽  
Biphasic Insulin ◽  
Biphasic Insulin Release ◽  
Ca2 Channels

A study on the development of biphasic insulin release and sensitivity to inhibitors has been performed using perifused rat pancreas at 19.5 days of gestation (3 days before birth) and at 3 days after birth. In the fetal pancreas, 16.7 mM glucose caused a marked stimulation of insulin release that did not, however, manifest a biphasic response and was not inhibited by verapamil, a Ca2+ channel blocker. This suggested that the immature response was due to either a lack of voltage-dependent Ca2+ channels or their failure to open in response to glucose. Depolarizing concentrations of KCl stimulated insulin release, which was inhibited by verapamil, demonstrating that functional Ca2+ channels were present. In the presence of 16.7 mM glucose, quinine, which blocks glucose-sensitive k+ channels, potentiated the response of the fetal pancreas that now became sensitive to verapamil, demonstrating that functional K+ channels were also present in the fetal pancreatic beta-cell. The immaturity of the response is not due specifically to a defect in glucose metabolism; rather the metabolism of nutrient secretagogues fails to couple with the K+ channel in the fetal islet and thus fails to depolarize the beta-cell membrane. Three days after birth the pattern of response to high glucose is biphasic. Insulin release in fetal pancreas was inhibited by epinephrine and somatostatin.

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