COPII-Dependent ER Export: A Critical Component of Insulin Biogenesis and β-Cell ER Homeostasis

Defects in the β-cells secretion system are well-described in Type 2 diabetes (T2D), including reduced insulin storage and impaired proinsulin processing; however, the cellular mechanisms underlying these secretory defects and the contribution of chronic hyperglycemia to this process remain poorly understood. In this study, we provide evidence that oxidative protein folding in the endoplasmic reticulum (ER) is perturbed in models of β-cell dysfunction, leading to delays in proinsulin trafficking and insulin granule formation. Using an in situ fluorescent pulse-chase labeling strategy and APEX2-based proximity labeling, we demonstrate that enriched interactions of proinsulin with ER oxidoreductases coincides with a delay in proinsulin ER export. Furthermore, our data show that proinsulin ER export can be regulated by metabolically-derived NADPH and reducing equivalent (glutathione) availability. Together, these data highlight an emerging role for nutrient metabolism and mitochondrial dysfunction in the maladaptive remodeling of the β-cells secretory pathway during the decline of β-cell function in T2D.

Download Full-text

Adipokines as key players in β cell function and failure

Clinical Science ◽

10.1042/cs20190523 ◽

2019 ◽

Vol 133 (22) ◽

pp. 2317-2327 ◽

Cited By ~ 3

Author(s):

Nicolás Gómez-Banoy ◽

James C. Lo

Keyword(s):

Metabolic Diseases ◽

Cell Function ◽

Whole Body ◽

Pancreatic Β Cell ◽

Β Cell ◽

Cell Axis ◽

Β Cell Function ◽

Prevalence Of Obesity ◽

Specific Factors ◽

Whole Body Metabolism

Abstract The growing prevalence of obesity and its related metabolic diseases, mainly Type 2 diabetes (T2D), has increased the interest in adipose tissue (AT) and its role as a principal metabolic orchestrator. Two decades of research have now shown that ATs act as an endocrine organ, secreting soluble factors termed adipocytokines or adipokines. These adipokines play crucial roles in whole-body metabolism with different mechanisms of action largely dependent on the tissue or cell type they are acting on. The pancreatic β cell, a key regulator of glucose metabolism due to its ability to produce and secrete insulin, has been identified as a target for several adipokines. This review will focus on how adipokines affect pancreatic β cell function and their impact on pancreatic β cell survival in disease contexts such as diabetes. Initially, the “classic” adipokines will be discussed, followed by novel secreted adipocyte-specific factors that show therapeutic promise in regulating the adipose–pancreatic β cell axis.

Download Full-text

The Biology of the Pancreatic β-Cell

10.1016/s1569-2558(08)x6007-2 ◽

1999 ◽

Keyword(s):

Pancreatic Β Cell ◽

Β Cell

Download Full-text

The Unique Contribution of Positive Orientation to Optimal Functioning

European Psychologist ◽

10.1027/1016-9040/a000070 ◽

2012 ◽

Vol 17 (1) ◽

pp. 44-54 ◽

Cited By ~ 46

Author(s):

Guido Alessandri ◽

Gian Vittorio Caprara ◽

John Tisak

Keyword(s):

Psychological Functioning ◽

Well Being ◽

Unique Contribution ◽

Critical Component ◽

Positive Orientation ◽

Cross Sectional ◽

Common Mode ◽

Optimal Functioning

Literature documents that the judgments people hold about themselves, their life, and their future are important ingredients of their psychological functioning and well-being, and are commonly related to each other. In this paper, results from a large cross-sectional sample (N = 1,331, 48% males) are presented attesting to the hypothesis that evaluations about oneself, one’s life, and one’s future rest on a common mode of viewing experiences named “Positive Orientation.” These results corroborate the utility of the new construct as a critical component of individuals’ well functioning.

Download Full-text

Conscious and Unconscious Reward Cues Can Affect a Critical Component of Executive Control

Experimental Psychology (formerly Zeitschrift für Experimentelle Psychologie) ◽

10.1027/1618-3169/a000104 ◽

2011 ◽

Vol 58 (5) ◽

pp. 370-375 ◽

Cited By ~ 23

Author(s):

Rémi L. Capa ◽

Gaëlle M. Bustin ◽

Axel Cleeremans ◽

Michel Hansenne

Keyword(s):

Correct Response ◽

Executive Control ◽

Critical Component ◽

Arithmetic Operations ◽

Component Process

The present study investigates whether updating an important function of executive control can be driven by unconscious reward cues. Participants had to memorize several numbers and update those numbers independently according to a sequence of arithmetic operations. At the beginning of each trial, a reward (1 euro or 5 cents) was presented, either subliminally or supraliminally. Participants could earn the reward if they found the correct response on the updating task. Results showed better performance when a high (conscious or unconscious) reward was at stake compared to a low reward. This suggests that subliminal information can influence a component process of executive control traditionally thought to require consciousness.

Download Full-text