β Cell and Autophagy: What Do We Know?

Abstract

Pancreatic β cells are central to glycemic regulation through insulin production. Studies show autophagy as an essential process in β cell function and fate. Autophagy is a catabolic cellular process that regulates cell homeostasis by recycling surplus or damaged cell components. Impaired autophagy results in β cell loss of function and apoptosis and, as a result, diabetes initiation and progress. It has been shown that in response to endoplasmic reticulum stress, inflammation, and high metabolic demands, autophagy affects β cell function, insulin synthesis, and secretion. This review highlights recent evidence regarding how autophagy can affect β cells’ fate in the pathogenesis of diabetes. Furthermore, we discuss the role of important intrinsic and extrinsic autophagy modulators, which can lead to β cell failure.

Characterizing poorly controlled type 2 diabetes using 1H-NMR metabolomics

“…The latter then progressively results in a loss of membrane potential, and the subsequent formation of secondary necrotic cells, leading to the leakage of cellular constituents (Kim & Lee, 2010 ; Sachet et al, 2017 ), explaining the observed increase in proteins and other cell membrane constituents (Sachet et al, 2017 ), such as phospholipid derivatives (choline, myo-inositol (Chaurio et al, 2009 ) and glycan structural components (mannose, N-acetylglucosamine (Rapoport & Pendu, 1999 ) in these poorly controlled type 2 diabetes patients. In contrast to this, several studies have also reported hyperactivation of autophagy in type 2 diabetes patients, as a compensatory mechanism to recycle various cellular contents for the production of adenosine triphosphate during hypoglycemic/fasting states (Denton & Kumar, 2019 ; Mohammadi-Motlagh et al, 2023 ; Yang et al, 2017 ). Interestingly, it has also been suggested that the increased autophagy that occurs in diabetes patients β-cells may also be caused by metformin treatment (Jiang et al, 2014 ), and a secondary inhibition of mTORc1 (Blandino-Rosano et al, 2017 ).…”

Dysmetabolic comorbidities and non-alcoholic fatty liver disease: a stairway to metabolic dysfunction-associated steatotic liver disease

“…NAFLD is related to decreased adult lung function and obstructive sleep apnea syndrome development [101] , while data on MASLD are lacking. MASLD patients have a higher risk of developing sarcopenia due to nutritional disorders, gut dysbiosis, and insulin resistance [102,103] . A mutual relationship between sarcopenia and insulin resistance exists due to mammalian target complex 1 rapamycin (mTORC1) action in skeletal muscle.…”

Mitochondrial Dynamics and Insulin Secretion

“…Drp1 also plays a critical role in the regulation of mitophagy as shown in Figure 2 , thus helping to maintain mitochondrial integrity and function necessary for cell survival [ 118 , 119 , 120 , 121 ]. Previous studies also demonstrated mitochondrial fission followed by selective fusion and elimination of dysfunctional mitochondria through mitophagy [ 71 ].…”