The role of growth hormone receptor in β cell function

Wang, Shuang; Wu, Jin; Wang, Ning; Zeng, Li; Wu, Yingjie

doi:10.1016/j.ghir.2017.08.002

Cited by 10 publications

(5 citation statements)

References 97 publications

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“…In this experiment, we also observed that hGH increased insulin secretion (Figure S3D,E). This observation was consistent with the published studies showing that GH directly increases insulin secretion from βcells (reviewed 108 ). Collectively, these outcomes suggest that using an hGH reporter as a surrogate for insulin secretion is not ideal.…”

Section: Discussionsupporting

confidence: 93%

Genetic ablation of synaptotagmin‐9 alters tomosyn‐1 function to increase insulin secretion from pancreatic β‐cells improving glucose clearance

et al. 2023

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Stimulus‐coupled insulin secretion from the pancreatic islet β‐cells involves the fusion of insulin granules to the plasma membrane (PM) via SNARE complex formation—a cellular process key for maintaining whole‐body glucose homeostasis. Less is known about the role of endogenous inhibitors of SNARE complexes in insulin secretion. We show that an insulin granule protein synaptotagmin‐9 (Syt9) deletion in mice increased glucose clearance and plasma insulin levels without affecting insulin action compared to the control mice. Upon glucose stimulation, increased biphasic and static insulin secretion were observed from ex vivo islets due to Syt9 loss. Syt9 colocalizes and binds with tomosyn‐1 and the PM syntaxin‐1A (Stx1A); Stx1A is required for forming SNARE complexes. Syt9 knockdown reduced tomosyn‐1 protein abundance via proteasomal degradation and binding of tomosyn‐1 to Stx1A. Furthermore, Stx1A‐SNARE complex formation was increased, implicating Syt9‐tomosyn‐1‐Stx1A complex is inhibitory in insulin secretion. Rescuing tomosyn‐1 blocked the Syt9‐knockdown‐mediated increases in insulin secretion. This shows that the inhibitory effects of Syt9 on insulin secretion are mediated by tomosyn‐1. We report a molecular mechanism by which β‐cells modulate their secretory capacity rendering insulin granules nonfusogenic by forming the Syt9‐tomosyn‐1‐Stx1A complex. Altogether, Syt9 loss in β‐cells decreases tomosyn‐1 protein abundance, increasing the formation of Stx1A‐SNARE complexes, insulin secretion, and glucose clearance. These outcomes differ from the previously published work that identified Syt9 has either a positive or no effect of Syt9 on insulin secretion. Future work using β‐cell‐specific deletion of Syt9 mice is key for establishing the role of Syt9 in insulin secretion.

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Section: Discussionsupporting

confidence: 93%

Genetic ablation of synaptotagmin‐9 alters tomosyn‐1 function to increase insulin secretion from pancreatic β‐cells improving glucose clearance

et al. 2023

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“…Another possibility is that GHR ablation may have occurred in pancreatic islets since both LepR and nestin are expressed in pancreatic islets (16,20,43,57,76,85). Furthermore, it is well known that GHR regulates beta-cell function (56,63,78,80). However, previous studies have shown that GHR ablation in LepR cells does not reduce Ghr mRNA levels in the pancreas (13), and nestin-expressing cells are not pancreatic endocrine cells that produce insulin, glucagon, somatostatin, or pancreatic polypeptide (20,76,85).…”

Section: Discussionmentioning

confidence: 99%

Central growth hormone action regulates metabolism during pregnancy

Teixeira

Couto

Furigo

et al. 2019

American Journal of Physiology-Endocrinology and Metabolism

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The maternal organism undergoes numerous metabolic adaptations to become prepared for the demands associated with the coming offspring. These metabolic adaptations involve changes induced by several hormones that act at multiple levels, ultimately influencing energy and glucose homeostasis during pregnancy and lactation. Previous studies have shown that central growth hormone (GH) action modulates glucose and energy homeostasis. However, whether central GH action regulates metabolism during pregnancy and lactation is still unknown. In the present study, we generated mice carrying ablation of GH receptor (GHR) in agouti-related protein (AgRP)–expressing neurons, in leptin receptor (LepR)–expressing cells or in the entire brain to investigate the role played by central GH action during pregnancy and lactation. AgRP-specific GHR ablation led to minor metabolic changes during pregnancy and lactation. However, while brain-specific GHR ablation reduced food intake and body adiposity during gestation, LepR GHR knockout (KO) mice exhibited increased leptin responsiveness in the ventromedial nucleus of the hypothalamus during late pregnancy, although their offspring showed reduced growth rate. Additionally, both Brain GHR KO and LepR GHR KO mice had lower glucose tolerance and glucose-stimulated insulin secretion during pregnancy, despite presenting increased insulin sensitivity, compared with control pregnant animals. Our findings revealed that during pregnancy central GH action regulates food intake, fat retention, as well as the sensitivity to insulin and leptin in a cell-specific manner. Together, the results suggest that GH acts in concert with other “gestational hormones” to prepare the maternal organism for the metabolic demands of the offspring.

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“…GH is an important promoter of stem cell activation, cell growth and differentiation (34). GHR is a class 1 receptor to which GH binds to promote cell growth (35). A previous study demonstrated that MSM could enhance GH signaling by regulating the Jak2/STAT5b pathway (36).…”

Section: Discussionmentioning

confidence: 99%

Non‑toxic sulfur enhances growth hormone signaling through the JAK2/STAT5b/IGF‑1 pathway in C2C12 cells

Kang

et al. 2019

Int J Mol Med

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Insulin-like growth factor-1 (IGF-1) regulates cell growth, glucose uptake and protein metabolism, and is required for growth hormone (GH) signaling-mediated insulin production and secretion. IGF1 expression is associated with STAT5, which binds to a region (TTcNNNGAA) of the gene. Although sulfur is used in various fields, the toxicity of this element is a significant disadvantage as it causes indigestion, vomiting, diarrhea, pain and migraine. Therefore, it is difficult to conduct in vitro experiments to directly determine the effects of dietary sulfur. Additionally, it is difficult to dissolve non-toxic sulfur (NTS). The present study aimed to identify the role of NTS in GH signaling as a Jak2/STAT5b/IGF-1 pathway regulator. MTT assay was used to identify an optimum NTS concentration for c2c12 mouse muscle cells. Western blotting, RT-PcR, chromatin immunoprecipitation, overexpression and small interfering RNA analyses were performed. NTS was dissolved in 1 mg/ml dMSO and could be used in vitro. Therefore, the present study determined whether NTS induced mouse muscle cell growth via GH signaling. NTS notably increased STAT5b binding to the Igf1 promoter. NTS also promoted GH signaling by upregulating GH receptor expression, similar to GH treatment. NTS enhanced GH signaling by regulating Jak2/STAT5b/IGF-1 signaling pathway factor expression in C2C12 mouse muscle cells. Thus, NTS may be used as a GH-enhancing growth stimulator.

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The role of growth hormone receptor in β cell function

Cited by 10 publications

References 97 publications

Genetic ablation of synaptotagmin‐9 alters tomosyn‐1 function to increase insulin secretion from pancreatic β‐cells improving glucose clearance

Genetic ablation of synaptotagmin‐9 alters tomosyn‐1 function to increase insulin secretion from pancreatic β‐cells improving glucose clearance

Central growth hormone action regulates metabolism during pregnancy

Non‑toxic sulfur enhances growth hormone signaling through the JAK2/STAT5b/IGF‑1 pathway in C2C12 cells

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