Rapid Ca2+ influx and diacyllycerol synthesis in growth hormone-mediated islet b-cell mitogenesis

• Growth hormone (GH) is an important mitogenic stimulus for the insulin-producing β-cell. We investigated the effects of GH on Ca2+ handling and diacylglycerol (DAG) and cAMP formation in the β-cell. GH elicited a rapid increase in the cytoplasmic free [Ca2+], which required extracellular Ca2+ and was also blocked by pertussis toxin or protein kinase C (PKC) inhibition. GH also elevated islet DAG content, which should lead to PKC activation. Pertussis toxin and PKC inhibitors obliterated the mitogenicity of GH, suggesting involvement of GTP-binding proteins. PKC activation stimulated β-cell proliferation, and it also activated phospholipase D. Islet cAMP content was not elevated by GH. Addition of a specific protein kinase A antagonist failed to influence the mitogenicity of GH, whereas a stimulatory cAMP agonist stimulated β-cell replication. We conclude that GH rapidly increases the β-cell cytoplasmic free [Ca2+] and also evokes a similar increase in DAG content via a phosphatidylcholine-specific phospholipase C, but does not affect mitogen-activated protein kinases, phospholipase D, or the cAMP signaling pathway. This rise in DAG may be of importance in translation of the stimulatory signal of GH into a proliferative response by the β-cell, which seems to occur through GTP-binding proteins and PKC-dependent mechanisms.

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MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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