scholarly journals Dynamin 2 regulates biphasic insulin secretion and plasma glucose homeostasis

2015 ◽  
Vol 125 (11) ◽  
pp. 4026-4041 ◽  
Author(s):  
Fan Fan ◽  
Chen Ji ◽  
Yumei Wu ◽  
Shawn M. Ferguson ◽  
Natalia Tamarina ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Homeostasis ◽  
Plasma Glucose ◽  
Biphasic Insulin ◽  
Biphasic Insulin Secretion ◽  
Dynamin 2

Dynamics of glucose-induced insulin secretion in normal human islets

2015 ◽  
Vol 309 (7) ◽  
pp. E640-E650 ◽  
Author(s):  
Jean-Claude Henquin ◽  
Denis Dufrane ◽  
Julie Kerr-Conte ◽  
Myriam Nenquin
Keyword(s):  
Insulin Secretion ◽  
Stimulation Index ◽  
Human Islets ◽  
Diabetic Patients ◽  
Second Phase ◽  
Biphasic Insulin ◽  
Biphasic Insulin Secretion ◽  
Normal Human ◽  
Second Phases

The biphasic pattern of glucose-induced insulin secretion is altered in type 2 diabetes. Impairment of the first phase is an early sign of β-cell dysfunction, but the underlying mechanisms are still unknown. Their identification through in vitro comparisons of islets from diabetic and control subjects requires characterization and quantification of the dynamics of insulin secretion by normal islets. When perifused normal human islets were stimulated with 15 mmol/l glucose (G15), the proinsulin/insulin ratio in secretory products rapidly and reversibly decreased (∼50%) and did not reaugment with time. Switching from prestimulatory G3 to G6–G30 induced biphasic insulin secretion with flat but sustained (2 h) second phases. Stimulation index reached 6.7- and 3.6-fold for the first and second phases induced by G10. Concentration dependency was similar for both phases, with half-maximal and maximal responses at G6.5 and G15, respectively. First-phase response to G15–G30 was diminished by short (30–60 min) prestimulation in G6 (vs. G3) and abolished by prestimulation in G8, whereas the second phase was unaffected. After 1–2 days of culture in G8 (instead of G5), islets were virtually unresponsive to G15. In both settings, a brief return to G3–G5 or transient omission of CaCl2 restored biphasic insulin secretion. Strikingly, tolbutamide and arginine evoked immediate insulin secretion in islets refractory to glucose. In conclusion, we quantitatively characterized the dynamics of glucose-induced insulin secretion in normal human islets and showed that slight elevation of prestimulatory glucose reversibly impairs the first phase, which supports the view that the similar impairment in type 2 diabetic patients might partially be a secondary phenomenon.

scholarly journals Assessment of the Metabolic Pathways Associated With Glucose-Stimulated Biphasic Insulin Secretion

Endocrinology ◽  
2014 ◽  
Vol 155 (5) ◽  
pp. 1653-1666 ◽  
Author(s):  
Mei Huang ◽  
Jamie W. Joseph
Keyword(s):  
Insulin Secretion ◽  
Time Course ◽  
Tricarboxylic Acid Cycle ◽  
Global Analysis ◽  
Tricarboxylic Acid ◽  
Second Phase ◽  
Data Set ◽  
Negatively Associated ◽  
Biphasic Insulin ◽  
Biphasic Insulin Secretion

Biphasic glucose-stimulated insulin secretion involves a rapid first phase followed by a prolonged second phase of insulin secretion. The biochemical pathways that control these 2 phases of insulin secretion are poorly defined. In this study, we used a gas chromatography mass spectroscopy-based metabolomics approach to perform a global analysis of cellular metabolism during biphasic insulin secretion. A time course metabolomic analysis of the clonal β-cell line 832/13 cells showed that glycolytic, tricarboxylic acid, pentose phosphate pathway, and several amino acids were strongly correlated to biphasic insulin secretion. Interestingly, first-phase insulin secretion was negatively associated with l-valine, trans-4-hydroxy-l-proline, trans-3-hydroxy-l-proline, dl-3-aminoisobutyric acid, l-glutamine, sarcosine, l-lysine, and thymine and positively with l-glutamic acid, flavin adenine dinucleotide, caprylic acid, uridine 5′-monophosphate, phosphoglycerate, myristic acid, capric acid, oleic acid, linoleic acid, and palmitoleic acid. Tricarboxylic acid cycle intermediates pyruvate, α-ketoglutarate, and succinate were positively associated with second-phase insulin secretion. Other metabolites such as myo-inositol, cholesterol, dl-3-aminobutyric acid, and l-norleucine were negatively associated metabolites with the second-phase of insulin secretion. These studies provide a detailed analysis of key metabolites that are either negatively or positively associated with biphasic insulin secretion. The insights provided by these data set create a framework for planning future studies in the assessment of the metabolic regulation of biphasic insulin secretion.

Triggering and Augmentation Mechanisms, Granule Pools, and Biphasic Insulin Secretion

Diabetes ◽  
2002 ◽  
Vol 51 (Supplement 1) ◽  
pp. S83-S90 ◽  
Author(s):  
T. K. Bratanova-Tochkova ◽  
H. Cheng ◽  
S. Daniel ◽  
S. Gunawardana ◽  
Y.-J. Liu ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Biphasic Insulin ◽  
Biphasic Insulin Secretion

Importance of Nonionic Signals for Glucose-Induced Biphasic Insulin Secretion

Diabetes ◽  
2002 ◽  
Vol 51 (Supplement 1) ◽  
pp. S96-S98 ◽  
Author(s):  
T. Aizawa ◽  
Y. Sato ◽  
M. Komatsu
Keyword(s):  
Insulin Secretion ◽  
Biphasic Insulin ◽  
Biphasic Insulin Secretion

scholarly journals Exocyst Sec5 Regulates Exocytosis of Newcomer Insulin Granules Underlying Biphasic Insulin Secretion

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e67561 ◽  
Author(s):  
Li Xie ◽  
Dan Zhu ◽  
Youhou Kang ◽  
Tao Liang ◽  
Yu He ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Biphasic Insulin ◽  
Insulin Granules ◽  
Biphasic Insulin Secretion ◽  
Newcomer Insulin Granules

Granule docking and cargo release in pancreatic β-cells

2008 ◽  
Vol 36 (3) ◽  
pp. 294-299 ◽  
Author(s):  
Sebastian Barg ◽  
Anders Lindqvist ◽  
Stefanie Obermüller
Keyword(s):  
Insulin Secretion ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Fusion Pore ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Isolated Pancreatic Islets ◽  
Biphasic Insulin ◽  
Biphasic Insulin Secretion

Biphasic insulin secretion is required for proper insulin action and is observed not only in vivo, but also in isolated pancreatic islets and even single β-cells. Late events in the granule life cycle are thought to underlie this temporal pattern. In the last few years, we have therefore combined live cell imaging and electrophysiology to study insulin secretion at the level of individual granules, as they approach the plasma membrane, undergo exocytosis and finally release their insulin cargo. In the present paper, we review evidence for two emerging concepts that affect insulin secretion at the level of individual granules: (i) the existence of specialized sites where granules dock in preparation for exocytosis; and (ii) post-exocytotic regulation of cargo release by the fusion pore.

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