scholarly journals Dynamin Is Functionally Coupled to Insulin Granule Exocytosis

2007 ◽  
Vol 282 (46) ◽  
pp. 33530-33536 ◽  
Author(s):  
Le Min ◽  
Yuk M. Leung ◽  
Alejandra Tomas ◽  
Robert T. Watson ◽  
Herbert Y. Gaisano ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Insulin Secretion ◽  
Human Growth Hormone ◽  
Fluorescent Protein ◽  
Protein Localization ◽  
Secretory Granules ◽  
Human Growth ◽  
Β Cell ◽  
Marked Inhibition ◽  
Insulin Granule

The insulin granule integral membrane protein marker phogrin-green fluorescent protein was co-localized with insulin in Min6B1 β-cell secretory granules but did not undergo plasma membrane translocation following glucose stimulation. Surprisingly, although expression of a dominant-interfering dynamin mutant (Dyn/K44A) inhibited transferrin receptor endocytosis, it had no effect on phogringreen fluorescent protein localization in the basal or secretagogue-stimulated state. By contrast, co-expression of Dyn/K44A with human growth hormone as an insulin secretory marker resulted in a marked inhibition of human growth hormone release by glucose, KCl, and a combination of multiple secretagogues. Moreover, serial pulse depolarization stimulated an increase in cell surface capacitance that was also blocked in cells expressing Dyn/K44A. Similarly, small interference RNA-mediated knockdown of dynamin resulted in marked inhibition of glucose-stimulated insulin secretion. Together, these data suggest the presence of a selective kiss and run mechanism of insulin release. Moreover, these data indicate a coupling between endocytosis and exocytosis in the regulation of β-cell insulin secretion.

Isolated human growth hormone deficiency. III. Insulin secretion in sexual ateliotic dwarfism

Metabolism ◽  
1968 ◽  
Vol 17 (11) ◽  
pp. 1005-1011 ◽  
Author(s):  
T.J. Merimee ◽  
D. Rabinowitz ◽  
D.L. Rimoin ◽  
V.A. McKusick
Keyword(s):  
Growth Hormone ◽  
Insulin Secretion ◽  
Growth Hormone Deficiency ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Hormone Deficiency

Involvement of JAK2 and Src kinase tyrosine phosphorylation in human growth hormone-stimulated increases in cytosolic free Ca2+ and insulin secretion

2006 ◽  
Vol 291 (3) ◽  
pp. C466-C475 ◽  
Author(s):  
Fan Zhang ◽  
Qimin Zhang ◽  
Anders Tengholm ◽  
Åke Sjöholm
Keyword(s):  
Growth Hormone ◽  
Insulin Secretion ◽  
Tyrosine Phosphorylation ◽  
Human Growth Hormone ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Src Kinase ◽  
Human Growth ◽  
Β Cells ◽  
Jak2 Inhibitor

We previously reported that human growth hormone (hGH) increases cytoplasmic Ca2+ concentration ([Ca2+]i) and proliferation in pancreatic β-cells (Sjöholm Å, Zhang Q, Welsh N, Hansson A, Larsson O, Tally M, and Berggren PO. J Biol Chem 275: 21033–21040, 2000) and that the hGH-induced rise in [Ca2+]i involves Ca2+-induced Ca2+ release facilitated by tyrosine phosphorylation of ryanodine receptors (Zhang Q, Kohler M, Yang SN, Zhang F, Larsson O, and Berggren PO. Mol Endocrinol 18: 1658–1669, 2004). Here we investigated the tyrosine kinases that convey the hGH-induced rise in [Ca2+]i and insulin release in BRIN-BD11 β-cells. hGH caused tyrosine phosphorylation of Janus kinase (JAK)2 and c-Src, events inhibited by the JAK2 inhibitor AG490 or the Src kinase inhibitor PP2. Although hGH-stimulated rises in [Ca2+]i and insulin secretion were completely abolished by AG490 and JAK2 inhibitor II, the inhibitors had no effect on insulin secretion stimulated by a high K+ concentration. Similarly, Src kinase inhibitor-1 and PP2, but not its inactive analog PP3, suppressed [Ca2+]i elevation and completely abolished insulin secretion stimulated by hGH but did not affect responses to K+. Ovine prolactin increased [Ca2+]i and insulin secretion to a similar extent as hGH, effects prevented by the JAK2 and Src kinase inhibitors. In contrast, bovine GH evoked a rise in [Ca2+]i but did not stimulate insulin secretion. Neither JAK2 nor Src kinase inhibitors influenced the effect of bovine GH on [Ca2+]i. Our study indicates that hGH stimulates rise in [Ca2+]i and insulin secretion mainly through activation of the prolactin receptor and JAK2 and Src kinases in rat insulin-secreting cells.

scholarly journals A fluorescent timer reporter enables sorting of insulin secretory granules by age

2020 ◽  
Vol 295 (27) ◽  
pp. 8901-8911 ◽  
Author(s):  
Belinda Yau ◽  
Lori Hays ◽  
Cassandra Liang ◽  
D. Ross Laybutt ◽  
Helen E. Thomas ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cell Function ◽  
Islet Cells ◽  
Ex Vivo ◽  
Secretory Granules ◽  
Β Cells ◽  
Β Cell ◽  
Short Period ◽  
Insulin Granule

Within the pancreatic β-cells, insulin secretory granules (SGs) exist in functionally distinct pools, displaying variations in motility as well as docking and fusion capability. Current therapies that increase insulin secretion do not consider the existence of these distinct SG pools. Accordingly, these approaches are effective only for a short period, with a worsening of glycemia associated with continued decline in β-cell function. Insulin granule age is underappreciated as a determinant for why an insulin granule is selected for secretion and may explain why newly synthesized insulin is preferentially secreted from β-cells. Here, using a novel fluorescent timer protein, we aimed to investigate the preferential secretion model of insulin secretion and identify how granule aging is affected by variation in the β-cell environment, such as hyperglycemia. We demonstrate the use of a fluorescent timer construct, syncollin-dsRedE5TIMER, which changes its fluorescence from green to red over 18 h, in both microscopy and fluorescence-assisted organelle-sorting techniques. We confirm that the SG-targeting construct localizes to insulin granules in β-cells and does not interfere with normal insulin SG behavior. We visualize insulin SG aging behavior in MIN6 and INS1 β-cell lines and in primary C57BL/6J mouse and nondiabetic human islet cells. Finally, we separated young and old insulin SGs, revealing that preferential secretion of younger granules occurs in glucose-stimulated insulin secretion. We also show that SG population age is modulated by the β-cell environment in vivo in the db/db mouse islets and ex vivo in C57BL/6J islets exposed to different glucose environments.

Insulin secretion in growth hormone—deficient adults: Effects of 24 months' therapy and five days' acute withdrawal of recombinant human growth hormone

Metabolism ◽  
1999 ◽  
Vol 48 (11) ◽  
pp. 1387-1396 ◽  
Author(s):  
Norshinah Kamarudin ◽  
Fen Lee Hew ◽  
Michael Christopher ◽  
Janet Alford ◽  
Christian Rantzau ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Insulin Secretion ◽  
Human Growth Hormone ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Acute Withdrawal

DYNAMICS OF INSULIN RELEASE BY PERFUSED HAMSTER (MESOCRICETUS AURATUS) PANCREASES: EFFECTS OF HYPOPHYSECTOMY, BOVINE AND HUMAN GROWTH HORMONE, AND PROLACTIN

1975 ◽  
Vol 65 (2) ◽  
pp. 245-251 ◽  
Author(s):  
DONALD L. CURRYt ◽  
LESLIE L. BENNETT ◽  
CHOH HAO LI
Keyword(s):  
Growth Hormone ◽  
Insulin Secretion ◽  
Steady State ◽  
Dynamic Response ◽  
Insulin Release ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Mesocricetus Auratus ◽  
Bovine Growth Hormone ◽  
Biphasic Pattern

SUMMARY The hamster exhibits a biphasic pattern of insulin secretion; however, the dynamic response differs qualitatively from that of the rat in that there is a steady-state second release phase. A marked attenuation of insulin secretion as a result of hypophysectomy was observed after 3 weeks, but not after 2 weeks. This depression of insulin secretion was restored to near or above normal levels by bovine growth hormone, human growth hormone, and prolactin.

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