Growth hormone signaling in pancreatic beta-cells--calcium handling regulated by growth hormone.
Deficiency in insulin secretion is a fundamental part in the pathogenesis of all forms of diabetes, determined by impaired secretory function and inadequate beta-cell mass. Growth hormone (GH) is a multifunctional hormone, involved in cellular metabolism, mitogenesis and differentiation. In pancreatic islets, GH is involved in maintaining beta-cell mass, stimulating islet hormone production and insulin secretion, and, therefore, plays a role in maintaining normal insulin sensitivity and glucose homeostasis. The intracellular events that convey the GH signal into various cellular responses remain incompletely understood. In this review, we discuss GH signaling in the beta-cells, with emphasis on Ca(2+) handling and insulin secretion regulated by human GH (hGH). hGH-stimulated rise in [Ca(2+)](i) is dependent on extracellular Ca(2+) and is mediated by Ca(2+)-induced Ca(2+) release (CICR) in the beta-cell. This process is triggered by hGH-stimulated activation of the non-receptor tyrosine kinases JAK2 and c-Src, which causes tyrosine phosphorylation of RyRs, resulting in sensitization of CICR. The rise in [Ca(2+)](i) elicited by hGH is associated with an enhanced insulin secretion, effects that are mediated mainly through the prolactin receptor. These mechanisms indicate that a rise in [Ca(2+)](i) elicited by activation of PRLR is JAK2-dependent and is associated with enhanced insulin secretion. In contrast, GH receptor-mediated increase in [Ca(2+)](i) is JAK2-independent and is dissociated from insulin secretion.
Zhang
Fan
F
Diabetes Research Center, Department of Clinical Science and Education, Karolinska Institutet, Stockholm South Hospital, SE-11883 Stockholm, Sweden.
Sjöholm
Ake
A
Zhang
Qimin
Q
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000378:metabolism; D015398:Signal Transduction
D011986:Receptors, Somatotropin; D013006:Growth Hormone; D002118:Calcium