Islet cilia and glucose homeostasis

Abstract

Diabetes is a growing pandemic affecting over ten percent of the U.S. population. Individuals with all types of diabetes exhibit glucose dysregulation due to altered function and coordination of pancreatic islets. Within the critical intercellular space in pancreatic islets, the primary cilium emerges as an important physical structure mediating cell-cell crosstalk and signal transduction. Many events leading to hormone secretion, including GPCR and second-messenger signaling, are spatiotemporally regulated at the level of the cilium. In this review, we summarize current knowledge of cilia action in islet hormone regulation and glucose homeostasis, focusing on newly implicated ciliary pathways that regulate insulin exocytosis and intercellular communication. We present evidence of key signaling proteins on islet cilia and discuss ways in which cilia might functionally connect islet endocrine cells with the non-endocrine compartments. These discussions aim to stimulate conversations regarding the extent of cilia-controlled glucose homeostasis in health and in metabolic diseases.

Beta cell primary cilia mediate somatostatin responsiveness via SSTR3

“…The primary cilium in pancreatic islet cells has emerged as a key locus of pancreas development and integration of hormone signaling. 26 , 27 We 28 and others 29 have shown that cilia-deficient beta cells have defective glucose-stimulated insulin secretion. At the organism level, deletion of beta cell cilia in mice leads to increased fasting blood glucose levels and impaired glucose tolerance without obesity that was further exacerbated by high fat diet.…”

A theoretical model of dietary lipid variance as the origin of primary ciliary dysfunction in preeclampsia

“…Classically, ciliopathies originate in gene mutations that code for proteins that are important in the formation or function of cilia ( Waters and Beales, 2011 ; Wheway et al, 2019 ; Focșa et al, 2021 ). However, recently, cilia have been implicated in conditions without clear genetic antecedents, such as obesity ( Wu et al, 2023 ), diabetes ( Liu et al, 2022 ; Melena and Hughes, 2022 ), neurodegenerative diseases ( Dhekne et al, 2018 ; Ki et al, 2021 ; Nguyen et al, 2021 ), cancer ( Kimura et al, 2023 ), psychiatric disorders ( Alhassen et al, 2021 ), autoimmune disorders ( Martínez-Hernández et al, 2019 ; Chen et al, 2021 ; Nishimura et al, 2021 ), and cardiovascular diseases ( Pala et al, 2018 ; Wang et al, 2021 ) including preeclampsia ( Wang et al, 2019a ; Ritter et al, 2020 ; Romberg et al, 2022 ).…”