Journal of Diabetes最新文献

Follicle-stimulating hormone (FSH), a classical hormone derived from the pituitary, primarily affects the gonads and regulates the reproductive process.¹ FSH consists of an α and a β subunit, with the β subunit specifically binding to its G protein-coupled receptor (GPCR), FSHR.² The FSHR mediates the transduction of the FSH-induced signal. According to the recent work published in Nature Communications, FSH, through its receptor, regulates glucose-stimulated insulin secretion (GSIS) in pancreatic islets, and high levels of FSH play important roles in postmenopausal diabetes in females.³

An increasing body of evidence has demonstrated that FSH and its receptor FSHR also have extragonadal effects, including the regulation of fat accumulation, bone mass, and cognitive function.^4-7 However, limited research has been focused on the effect of FSH on metabolism. The pancreas is an important endocrine organ in regulating glucose metabolism. First, the authors explored whether FSHR was expressed in pancreas. They identified the expression of FSHR in human pancreas, mouse pancreatic islets, and the mouse insulinoma cell line MIN6. The expression of FSHR in pancreatic islets strongly suggests an association between FSHR and the endocrine function. In order to explore the function of FSH and FSHR on pancreatic islets, the authors established a conventional Fshr^−/−(knockout [KO]) mouse model. Blocking FSH signaling through Fshr KO resulted in impaired glucose tolerance. In this model, Fshr KO led to an increase in serum FSH levels as well as a decrease in serum estrogen levels. Females with Fshr KO administrated with estrogen also displayed impaired glucose tolerance. Furthermore, the authors generated a mouse model with specific deletion of Fshr in the pancreas (Fshr CKO), which showed no significant alterations in serum FSH and estrogen levels. Similarly, female Fshr CKO mice exhibited impaired glucose tolerance. The phenotype of glucose intolerance was also observed in male mice with Fshr KO and CKO male mice.

Glucose intolerance is primarily caused by impaired insulin secretion and action. The authors evaluated peripheral insulin action and found there was no significant insulin resistance in Fshr KO and CKO mice. However, decreased insulin secretion was observed in Fshr KO and CKO mice. In vitro, treatment of mouse pancreatic islets and MIN6 cells with FSH did not result in any significant changes in Ins1 and Ins2 mRNA levels or insulin content, suggesting that the effect of FSH on glucose tolerance was due to insulin secretion, not insulin synthesis. Interestingly, the authors discovered that FSH alone, in the absence of glucose, did not stimulate insulin secretion. FSH regulated GSIS in a bell curve manner. FSH promoted GSIS as FSH levels increased within the range of <10 IU/L. However, the promoting effect on GSIS was in

Kisspeptins (KPs) are proteins that were first recognized to have antimetastatic action. Later, the critical role of this peptide in the regulation of reproduction was proved. In recent years, evidence has been accumulated supporting a role for KPs in regulating metabolic processes in a sexual dimorphic manner. It has been proposed that KPs regulate metabolism both indirectly via gonadal hormones and/or directly via the kisspeptin receptor in the brain, brown adipose tissue, and pancreas. The aim of the review is to provide both experimental and clinical evidence indicating that KPs are peptides linking metabolism and reproduction. We propose that KPs could be used as a potential target to treat both metabolic and reproductive abnormalities. Thus, we focus on the consequences of disruptions in KPs and their receptors in metabolic conditions such as diabetes, undernutrition, obesity, and reproductive disorders (hypogonadotropic hypogonadism and polycystic ovary syndrome). Data from both animal models and human subjects indicate that alterations in KPs in the case of metabolic imbalance lead also to disruptions in reproductive functions. Changes both in the hypothalamic and peripheral KP systems in animal models of the aforementioned disorders are discussed. Finally, an overview of current clinical studies involving KP in fertility and metabolism show fewer studies on metabolism (15%) and only one to date on both. Presented data indicate a dynamic and emerging field of KP studies as possible therapeutic targets in treatments of both reproductive and metabolic dysfunctions.

Although pancreas and islet cell transplantation are the only ways to prevent the late complications of insulin-dependent diabetes, a shortage of donors is a major obstacle to tissue and organ transplantation. Stem cell therapy is an effective treatment for diabetes and other pancreatic-related diseases, which can be achieved by inducing their differentiation into insulin-secreting cells. The liver is considered an ideal source of pancreatic cells due to its similar developmental origin and strong regenerative ability as the pancreas. This article reviews the traditional and emerging strategies using hepatocytes for pancreatic regenerative medicine and evaluates their advantages and challenges. Gene reprogramming and chemical reprogramming technologies are traditional strategies with potential to improve the efficiency and specificity of cell reprogramming and promote the transformation of hepatocytes into islet cells. At the same time, organoid technology, as an emerging strategy, has received extensive attention. Biomaterials provide a three-dimensional culture microenvironment for cells, which helps improve cell survival and differentiation efficiency. In addition, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing technology has brought new opportunities and challenges to the development of organoid technology.