Effects of Glucose on Insulin Release and on Intermediary Metabolism of Isolated Perifused Pancreatic Islets from Fed and Fasted Rats

ABSTRACT The rapid, short-lived efflux of inorganic 32P-orthophosphate that occurs when pre-labelled pancreatic islets are exposed to nutrient insulin secretagogues (the "phosphate flush") has been proposed to reflect some early step in β-cell secretory activation. In the present study, glucose-initiated phosphate efflux was studied during fasting. Pancreatic islets were isolated from fed and 48-h fasted rats by collagenase digestion. After pre-labelling with 32P-orthophosphate and basal perifusion with 0.5 mg/ml glucose, tissue analyses disclosed similar stores of radioactivity in the two groups of islets. Stimulatory perifusion with glucose at this time failed to promote insulin release from islets which had been secured from fasted donors although the "phosphate flush" was preserved. However, the characteristics of phosphate efflux were altered. Maximal glucose-induced phosphate release was greater with islets from fasted animals whereas phosphate release in response to low level stimulation with glucose was diminished. Accordingly, the dose-response curve for glucose-initiated phosphate efflux in islets from fasted rats was displaced to the right and compatible with a decreased sensitivity to glucose at the activation site for the "phosphate flush." Thus, while glucose is unable to enhance insulin release in vitro after fasting, glucose still elicits increased phosphate efflux. However, the phenomenon appears to be attended by an impaired responsiveness to activation by glucose, supporting the contention that some early step in the sequence of stimulus secretion coupling in the β-cell may be obtunded after food deprivation.

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Differential metabolic requirement for initiation and augmentation of insulin release by glucose: a study with rat pancreatic islets

Journal of Endocrinology ◽

10.1677/joe.0.1430497 ◽

1994 ◽

Vol 143 (3) ◽

pp. 497-503 ◽

Cited By ~ 8

Author(s):

F Ishihara ◽

T Aizawa ◽

N Taguchi ◽

Y Sato ◽

K Hashizume

Keyword(s):

Low Temperature ◽

Pancreatic Islets ◽

Insulin Release ◽

High Glucose ◽

Glucose Oxidation ◽

Glucose Utilization ◽

Incubation Temperature ◽

Islet Cells ◽

Metabolic Requirement ◽

Fasted Rats

Abstract Insulin release, glucose utilization (3H2O formation from [5-3H]glucose), and glucose oxidation (14CO2 formation from [4C(U)] glucose) were determined in pancreatic islets from 96-h fasted rats at 37 ° C and those from fed rats at 22 ° C, using the islets from fed rats incubated at 37 ° C as controls. In the islets from 96-h fasted rats and those from fed rats incubated at 22 ° C, we could not demonstrate significant insulin release in response to high glucose concentrations of up to 16·7 mmol/l. However, 16·7 mmol/l glucose clearly augmented insulin release caused by a depolarizing concentration (50 mmol/l) of K+ in these islets: i.e. 16·7 mmol/l glucose plus 50 mmol/l K+ produced significantly greater insulin release than 50 mmol/l K alone. Glucose utilization and oxidation by the islet cells were suppressed by 96-h fasting of the rats or by lowering the incubation temperature to 22 ° C, and depolarization with K at 50 mmol/l did not at all augment glucose utilization and oxidation by the islets. Thus we conclude that reduction of glucose metabohsm in islets from fasted rats and in those incubated at low temperature eliminated initiation, but not augmentation, of insulin release by 16·7 mmol/l glucose. The data indicate that the metabolic threshold for the initiation of insulin release is significantly higher than it is for the augmentation of release by glucose. Journal of Endocrinology (1994) 143, 497–503

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Potentiation of glucose-induced insulin release by glucose in the isolated pancreas of fed and fasted rats

Diabetes ◽

10.2337/diabetes.25.10.949 ◽

1976 ◽

Vol 25 (10) ◽

pp. 949-954 ◽

Cited By ~ 6

Author(s):

S. Efendic ◽

E. Cerasi ◽

R. Luft ◽

G. Gladnikoff

Keyword(s):

Insulin Release ◽

Isolated Pancreas ◽

Fasted Rats

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Phenytoin inhibition of insulin release. Studies on the involvement of Ca2+ fluxes in rat pancreatic islets

Diabetes ◽

10.2337/diabetes.31.3.265 ◽

1982 ◽

Vol 31 (3) ◽

pp. 265-269 ◽

Cited By ~ 2

Author(s):

E. G. Siegel ◽

D. Janjic ◽

C. B. Wollheim

Keyword(s):

Pancreatic Islets ◽

Insulin Release ◽

Rat Pancreatic Islets ◽

Release Studies

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Testosterone Rapidly Stimulates Insulin Release from Isolated Pancreatic Islets through a Non-genomic Dependent Mechanism

Hormone and Metabolic Research ◽

10.1055/s-2005-870575 ◽

2005 ◽

Vol 37 (11) ◽

pp. 662-665 ◽

Cited By ~ 25

Author(s):

M. L. Grillo ◽

A. P. Jacobus ◽

R. Scalco ◽

F. Amaral ◽

D. O. Rodrigues ◽

...

Keyword(s):

Pancreatic Islets ◽

Insulin Release ◽

Isolated Pancreatic Islets ◽

Dependent Mechanism

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Direct effect of parathyroid hormone on insulin secretion from pancreatic islets

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1990.258.6.e975 ◽

1990 ◽

Vol 258 (6) ◽

pp. E975-E984 ◽

Cited By ~ 5

Author(s):

G. Z. Fadda ◽

M. Akmal ◽

L. G. Lipson ◽

S. G. Massry

Keyword(s):

Insulin Secretion ◽

Parathyroid Hormone ◽

Pancreatic Islets ◽

Insulin Release ◽

Direct Effect ◽

Indirect Evidence ◽

Cytosolic Calcium ◽

Dependent Manner ◽

Stimulation Of

Indirect evidence indicates that parathyroid hormone (PTH) interacts with pancreatic islets and modulates their insulin secretion. This property of PTH has been implicated in the genesis of impaired insulin release in chronic renal failure. We examined the direct effect of PTH-(1-84) and PTH-(1-34) on insulin release using in vitro static incubation and dynamic perifusion of pancreatic islets from normal rats. Both moieties of the hormone stimulated in a dose-dependent manner glucose-induced insulin release but higher doses inhibited glucose-induced insulin release. This action of PTH was modulated by the calcium concentration in the media. The stimulatory effect of PTH was abolished by its inactivation and blocked by its antagonist [Tyr-34]bPTH-(7-34)NH2. PTH also augmented phorbol ester (TPA)-induced insulin release, stimulated adenosine 3',5'-cyclic monophosphate (cAMP) generation by pancreatic islets, and significantly increased (+50 +/- 2.7%, P less than 0.01) their cytosolic calcium. Verapamil inhibited the stimulatory effect of PTH on insulin release. The data show that 1) pancreatic islets are a PTH target and may have PTH receptors, 2) stimulation of glucose-induced insulin release by PTH is mediated by a rise in cytosolic calcium, 3) stimulation of cAMP production by PTH and a potential indirect activation of protein kinase C by PTH may also contribute to the stimulatory effect on glucose-induced insulin release, and 4) this action of PTH requires calcium in incubation or perifusion media.

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The possible mechanisms by which phanoside stimulates insulin secretion from rat islets

Journal of Endocrinology ◽

10.1677/joe.1.06948 ◽

2007 ◽

Vol 192 (2) ◽

pp. 389-394 ◽

Cited By ~ 26

Author(s):

Nguyen Khanh Hoa ◽

Åke Norberg ◽

Rannar Sillard ◽

Dao Van Phan ◽

Nguyen Duy Thuan ◽

...

Keyword(s):

Insulin Secretion ◽

B Cells ◽

Pancreatic Islets ◽

Insulin Release ◽

Pertussis Toxin ◽

Insulin Response ◽

Gk Rat ◽

Isolated Pancreatic Islets ◽

Gk Rats ◽

Rat Islets

We recently showed that phanoside, a gypenoside isolated from the plant Gynostemma pentaphyllum, stimulates insulin secretion from rat pancreatic islets. To study the mechanisms by which phanoside stimulates insulin secretion. Isolated pancreatic islets of normal Wistar (W) rats and spontaneously diabetic Goto-Kakizaki (GK) rats were batch incubated or perifused. At both 3.3 and 16.7 mM glucose, phanoside stimulated insulin secretion several fold in both W and diabetic GK rat islets. In perifusion of W islets, phanoside (75 and 150 μM) dose dependently increased insulin secretion that returned to basal levels when phanoside was omitted. When W rat islets were incubated at 3.3 mM glucose with 150 μM phanoside and 0.25 mM diazoxide to keep K-ATP channels open, insulin secretion was similar to that in islets incubated in 150 μM phanoside alone. At 16.7 mM glucose, phanoside-stimulated insulin secretion was reduced in the presence of 0.25 mM diazoxide (P<0.01). In W islets depolarized by 50 mM KCl and with diazoxide, phanoside stimulated insulin release twofold at 3.3 mM glucose but did not further increase the release at 16.7 mM glucose. When using nimodipine to block L-type Ca2+ channels in B-cells, phanoside-induced insulin secretion was unaffected at 3.3 mM glucose but decreased at 16.7 mM glucose (P<0.01). Pretreatment of islets with pertussis toxin to inhibit exocytotic Ge-protein did not affect insulin response to 150 μM phanoside. Phanoside stimulated insulin secretion from Wand GK rat islets. This effect seems to be exerted distal to K-ATP channels and L-type Ca2+ channels, which is on the exocytotic machinery of the B-cells.

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