scholarly journals Circadian Regulation of the Pancreatic Beta Cell

Endocrinology ◽  
2021 ◽  
Author(s):  
Nivedita Seshadri ◽  
Christine A Doucette

Abstract Beta cell dysfunction is central to the development of type 2 diabetes (T2D). In T2D, environmental and genetic influences can manifest beta cell dysfunction in many ways, including impaired glucose-sensing and secretion coupling mechanisms, insufficient adaptative responses to stress and aberrant beta cell loss through increased cell death and/or beta cell de-differentiation. In recent years, circadian disruption has emerged as an important environmental risk factor for T2D. In support of this, genetic disruption of the circadian timing system in rodents impairs insulin secretion and triggers diabetes development, lending important evidence that the circadian timing system is intimately connected to, and essential for the regulation of pancreatic beta cell function; however, the role of the circadian timing system in the regulation of beta cell biology is only beginning to be unravelled. Here, we review the recent literature that explores the importance of the pancreatic islet/beta cell circadian clock in the regulation of various aspects of beta cell biology, including transcriptional and functional control of daily cycles of insulin secretion capacity, regulation of postnatal beta cell maturation, and control of the adaptive responses of the beta cell to metabolic stress and acute injury.

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 512
Author(s):  
Yong Kyung Kim ◽  
Lori Sussel ◽  
Howard W. Davidson

The pancreatic beta cell is a highly specialized cell type whose primary function is to secrete insulin in response to nutrients to maintain glucose homeostasis in the body. As such, the beta cell has developed unique metabolic characteristics to achieve functionality; in healthy beta cells, the majority of glucose-derived carbons are oxidized and enter the mitochondria in the form of pyruvate. The pyruvate is subsequently metabolized to induce mitochondrial ATP and trigger the downstream insulin secretion response. Thus, in beta cells, mitochondria play a pivotal role in regulating glucose stimulated insulin secretion (GSIS). In type 2 diabetes (T2D), mitochondrial impairment has been shown to play an important role in beta cell dysfunction and loss. In type 1 diabetes (T1D), autoimmunity is the primary trigger of beta cell loss; however, there is accumulating evidence that intrinsic mitochondrial defects could contribute to beta cell susceptibility during proinflammatory conditions. Furthermore, there is speculation that dysfunctional mitochondrial responses could contribute to the formation of autoantigens. In this review, we provide an overview of mitochondrial function in the beta cells, and discuss potential mechanisms by which mitochondrial dysfunction may contribute to T1D pathogenesis.


2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Alessandra Puddu ◽  
Roberta Sanguineti ◽  
François Mach ◽  
Franco Dallegri ◽  
Giorgio Luciano Viviani ◽  
...  

The primary function of pancreatic beta-cells is to produce and release insulin in response to increment in extracellular glucose concentrations, thus maintaining glucose homeostasis. Deficient beta-cell function can have profound metabolic consequences, leading to the development of hyperglycemia and, ultimately, diabetes mellitus. Therefore, strategies targeting the maintenance of the normal function and protecting pancreatic beta-cells from injury or death might be crucial in the treatment of diabetes. This narrative review will update evidence from the recently identified molecular regulators preserving beta-cell mass and function recovery in order to suggest potential therapeutic targets against diabetes. This review will also highlight the relevance for novel molecular pathways potentially improving beta-cell dysfunction.


Diabetologia ◽  
2021 ◽  
Vol 64 (11) ◽  
pp. 2534-2549
Author(s):  
Nur Shabrina Amirruddin ◽  
Wei Xuan Tan ◽  
Yaw Sing Tan ◽  
Daphne Su-Lyn Gardner ◽  
Yong Mong Bee ◽  
...  

Diabetologia ◽  
2011 ◽  
Vol 54 (9) ◽  
pp. 2337-2346 ◽  
Author(s):  
D. Favre ◽  
G. Niederhauser ◽  
D. Fahmi ◽  
V. Plaisance ◽  
S. Brajkovic ◽  
...  

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