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.

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.

Effects of tetracaine on insulin release and calcium handling by rat pancreatic islets

1987 ◽  
Vol 252 (6) ◽  
pp. E727-E733
Author(s):  
S. M. el Motal ◽  
M. C. Pian-Smith ◽  
G. W. Sharp
Keyword(s):  
Tissue Culture ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Culture Conditions ◽  
Isolated Islets ◽  
Calcium Handling ◽  
Ca Channels ◽  
Rat Pancreatic Islets ◽  
Voltage Dependent ◽  
Stimulate Insulin Release

The effects of tetracaine on insulin release and 45Ca2+ handling by rat pancreatic islets have been studied under basal (2.8 mM glucose), glucose-stimulated (5.6, 8.3, and 16.7 mM glucose), and 3-isobutyl-1-methylxanthine (IBMX)-stimulated conditions. Islets were isolated by the use of collagenase and used either directly (freshly isolated islets) or after a period under tissue culture conditions. Tetracaine was found to stimulate insulin release under basal conditions, to inhibit glucose-stimulated insulin release, and to potentiate insulin release stimulated by IBMX. In studies on the mechanisms underlying these effects, tetracaine was found to decrease glucose-stimulated net retention of 45Ca2+ (by an action to block the voltage-dependent Ca channels) and to mobilize Ca2+ from intracellular stores. These two actions form the basis for the inhibition of glucose-stimulated insulin release, which depends heavily on Ca2+ entry via the voltage-dependent channels and the synergism with IBMX to potentiate release. No inhibition of IBMX-stimulated release occurs because IBMX does not use the voltage-dependent channels to raise intracellular Ca2+.

DIMA Replication in Pancreatic Islets and Adrenals in Diabetic Chinese Hamsters

1993 ◽  
Vol 39 (1-2) ◽  
pp. 67-72 ◽  
Author(s):  
Barbara J. Frankel ◽  
Olle Korsgren ◽  
Arne Andersson
Keyword(s):  
Pancreatic Islets ◽  
Chinese Hamsters ◽  
Diabetic Chinese Hamsters

Anaplerotic input is sufficient to induce time-dependent potentiation of insulin release in rat pancreatic islets

2004 ◽  
Vol 287 (5) ◽  
pp. E828-E833 ◽  
Author(s):  
Subhadra C. Gunawardana ◽  
Yi-Jia Liu ◽  
Michael J. MacDonald ◽  
Susanne G. Straub ◽  
Geoffrey W. G. Sharp
Keyword(s):  
Insulin Release ◽  
Tricarboxylic Acid Cycle ◽  
Acid Methyl Ester ◽  
Time Dependent ◽  
Second Phase ◽  
Acetyl Coa ◽  
Atp Production ◽  
Biphasic Insulin ◽  
Intracellular Ca ◽  
Biphasic Insulin Release

Nutrients that induce biphasic insulin release, such as glucose and leucine, provide acetyl-CoA and anaplerotic input in the β-cell. The first phase of release requires increased ATP production leading to increased intracellular Ca2+ concentration ([Ca2+]i). The second phase requires increased [Ca2+]i and anaplerosis. There is strong evidence to indicate that the second phase is due to augmentation of Ca2+-stimulated release via the KATP channel-independent pathway. To test whether the phenomenon of time-dependent potentiation (TDP) has similar properties to the ATP-sensitive K+ channel-independent pathway, we monitored the ability of different agents that provide acetyl-CoA and anaplerotic input or both of these inputs to induce TDP. The results show that anaplerotic input is sufficient to induce TDP. Interestingly, among the agents tested, the nonsecretagogue glutamine, the nonhydrolyzable analog of leucine aminobicyclo[2.2.1]heptane-2-carboxylic acid, and succinic acid methyl ester all induced TDP, and all significantly increased α-ketoglutarate levels in the islets. In conclusion, anaplerosis that enhances the supply and utilization of α-ketoglutarate in the tricarboxylic acid cycle appears to play an essential role in the generation of TDP.

Adrenergic Modification of Glucose-Induced Biphasic Insulin Release from Perifused Rat Pancreas

1971 ◽  
Vol 1 (4) ◽  
pp. 216-224 ◽  
Author(s):  
Ian M. Burr ◽  
Luc Balant ◽  
Werner Stauffacher ◽  
Albert E. Renold
Keyword(s):  
Insulin Release ◽  
Rat Pancreas ◽  
Biphasic Insulin ◽  
Biphasic Insulin Release

scholarly journals A Microfluidic Hanging-Drop-Based Islet Perifusion System for Studying Glucose-Stimulated Insulin Secretion From Multiple Individual Pancreatic Islets

2021 ◽  
Vol 9 ◽  
Author(s):  
Patricia Wu Jin ◽  
Nassim Rousset ◽  
Andreas Hierlemann ◽  
Patrick M. Misun
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Sampling Interval ◽  
Liquid Volume ◽  
High Temporal Resolution ◽  
Diabetes Research ◽  
Hanging Drop ◽  
Biphasic Insulin Release ◽  
Glucose Stimulated Insulin Secretion

Islet perifusion systems can be used to monitor the highly dynamic insulin release of pancreatic islets in glucose-stimulated insulin secretion (GSIS) assays. Here, we present a new generation of the microfluidic hanging-drop-based islet perifusion platform that was developed to study the alterations in insulin secretion dynamics from single pancreatic islet microtissues at high temporal resolution. The platform was completely redesigned to increase experimental throughput and to reduce operational complexity. The experimental throughput was increased fourfold by implementing a network of interconnected hanging drops, which allows for performing GSIS assays with four individual islet microtissues in parallel with a sampling interval of 30 s. We introduced a self-regulating drop-height mechanism that enables continuous flow and maintains a constant liquid volume in the chip, which enables simple and robust operation. Upon glucose stimulation, reproducible biphasic insulin release was simultaneously observed from all islets in the system. The measured insulin concentrations showed low sample-to-sample variation as a consequence of precise liquid handling with stable drop volumes, equal flow rates in the channels, and accurately controlled sampling volumes in all four drops. The presented device will be a valuable tool in islet and diabetes research for studying dynamic insulin secretion from individual pancreatic islets.

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