scholarly journals Integrated In Vivo Quantitative Proteomics and Nutrient Tracing Reveals Age-Related Metabolic Rewiring of Pancreatic β Cell Function

Cell Reports ◽  
2018 ◽  
Vol 25 (10) ◽  
pp. 2904-2918.e8 ◽  
Author(s):  
Matthew Wortham ◽  
Jacqueline R. Benthuysen ◽  
Martina Wallace ◽  
Jeffrey N. Savas ◽  
Francesca Mulas ◽  
...  
Keyword(s):  
Quantitative Proteomics ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Age Related ◽  
Β Cell Function

scholarly journals Integrated in vivo quantitative proteomics and nutrient tracing reveals age-related metabolic rewiring of pancreatic β-cell function

2018 ◽  
Author(s):  
Matthew Wortham ◽  
Jacqueline R. Benthuysen ◽  
Martina Wallace ◽  
Jeffrey N. Savas ◽  
Francesca Mulas ◽  
...  
Keyword(s):  
Cell Function ◽  
Coupling Factor ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Age Related ◽  
Β Cell Function ◽  
One Year ◽  
Old Mice ◽  
Age Related Changes

SummaryPancreatic β-cell physiology changes substantially throughout life; yet, the mechanisms that drive these changes are poorly understood. Here, we performed comprehensive in vivo quantitative proteomic profiling of pancreatic islets from adolescent and one-year-old mice. The analysis revealed striking differences in abundance of enzymes controlling glucose metabolism. We show that these changes in protein abundance are associated with higher activities of glucose metabolic enzymes involved in coupling factor generation as well as increased activity of the coupling factor-dependent amplifying pathway of insulin secretion. Nutrient tracing and targeted metabolomics demonstrated accelerated accumulation of glucose-derived metabolites and coupling factors in islets from one-year-old mice, indicating that age-related changes in glucose metabolism contribute to improved glucose-stimulated insulin secretion with age. Together, our study provides the first in-depth characterization of age-related changes in the islet proteome and establishes metabolic rewiring as an important mechanism for age-associated changes in β-cell function.

scholarly journals The Estrogenic Effect of Bisphenol A Disrupts Pancreatic β-Cell Function In Vivo and Induces Insulin Resistance

2006 ◽  
Vol 114 (1) ◽  
pp. 106-112 ◽  
Author(s):  
Paloma Alonso-Magdalena ◽  
Sumiko Morimoto ◽  
Cristina Ripoll ◽  
Esther Fuentes ◽  
Angel Nadal
Keyword(s):  
Insulin Resistance ◽  
Bisphenol A ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Estrogenic Effect ◽  
Β Cell Function

scholarly journals The Angiotensin-(1–7)/Mas Axis Improves Pancreatic β-Cell Function in Vitro and in Vivo

Endocrinology ◽  
2016 ◽  
Vol 157 (12) ◽  
pp. 4677-4690 ◽  
Author(s):  
Anika Sahr ◽  
Carmen Wolke ◽  
Jonas Maczewsky ◽  
Peter Krippeit-Drews ◽  
Anja Tetzner ◽  
...  
Keyword(s):  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Β Cell Function

Lipid-induced pancreatic β-cell dysfunction: focus on in vivo studies

2011 ◽  
Vol 300 (2) ◽  
pp. E255-E262 ◽  
Author(s):  
Adria Giacca ◽  
Changting Xiao ◽  
Andrei I. Oprescu ◽  
Andre C. Carpentier ◽  
Gary F. Lewis
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Β Cell Function

The phenomenon of lipid-induced pancreatic β-cell dysfunction (“lipotoxicity”) has been very well documented in numerous in vitro experimental systems and has become widely accepted. In vivo demonstration of β-cell lipotoxicity, on the other hand, has not been consistently demonstrated, and there remains a lack of consensus regarding the in vivo effects of chronically elevated free fatty acids (FFA) on β-cell function. Much of the disagreement relates to how insulin secretion is quantified in vivo and in particular whether insulin secretion is assessed in relation to whole body insulin sensitivity, which is clearly reduced by elevated FFA. By correcting for changes in in vivo insulin sensitivity, we and others have shown that prolonged elevation of FFA impairs β-cell secretory function. Prediabetic animal models and humans with a positive family history of type 2 diabetes are more susceptible to this impairment, whereas those with severe impairment of β-cell function (such as individuals with type 2 diabetes) demonstrate no additional impairment of β-cell function when FFA are experimentally raised. Glucolipotoxicity (i.e., the combined β-cell toxicity of elevated glucose and FFA) has been amply demonstrated in vitro and in some animal studies but not in humans, perhaps because there are limitations in experimentally raising plasma glucose to sufficiently high levels for prolonged periods of time. We and others have shown that therapies directed toward diminishing oxidative stress and ER stress have the potential to reduce lipid-induced β-cell dysfunction in animals and humans. In conclusion, lipid-induced pancreatic β-cell dysfunction is likely to be one contributor to the complex array of genetic and metabolic insults that result in the relentless decline in pancreatic β-cell function in those destined to develop type 2 diabetes, and mechanisms involved in this lipotoxicity are promising therapeutic targets.

scholarly journals Islet-on-a-chip for the study of pancreatic β-cell function

2021 ◽  
Author(s):  
Júlia Rodríguez-Comas ◽  
Javier Ramón-Azcón
Keyword(s):  
Cell Biology ◽  
Cell Function ◽  
Public Health Problem ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Technological Advances ◽  
Significant Public Health ◽  
Β Cell Function

AbstractDiabetes mellitus is a significant public health problem worldwide. It encompasses a group of chronic disorders characterized by hyperglycemia, resulting from pancreatic islet dysfunction or as a consequence of insulin-producing β-cell death. Organ-on-a-chip platforms have emerged as technological systems combining cell biology, engineering, and biomaterial technological advances with microfluidics to recapitulate a specific organ’s physiological or pathophysiological environment. These devices offer a novel model for the screening of pharmaceutical agents and to study a particular disease. In the field of diabetes, a variety of microfluidic devices have been introduced to recreate native islet microenvironments and to understand pancreatic β-cell kinetics in vitro. This kind of platforms has been shown fundamental for the study of the islet function and to assess the quality of these islets for subsequent in vivo transplantation. However, islet physiological systems are still limited compared to other organs and tissues, evidencing the difficulty to study this “organ” and the need for further technological advances. In this review, we summarize the current state of islet-on-a-chip platforms that have been developed so far. We recapitulate the most relevant studies involving pancreatic islets and microfluidics, focusing on the molecular and cellular-scale activities that underlie pancreatic β-cell function.

Tributyltin exposure at noncytotoxic doses dysregulates pancreatic β-cell function in vitro and in vivo

2017 ◽  
Vol 91 (9) ◽  
pp. 3135-3144 ◽  
Author(s):  
Ya-Wen Chen ◽  
Kuo-Cheng Lan ◽  
Jing-Ren Tsai ◽  
Te-I Weng ◽  
Ching-Yao Yang ◽  
...  
Keyword(s):  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Β Cell Function

Adipokines as key players in β cell function and failure

2019 ◽  
Vol 133 (22) ◽  
pp. 2317-2327 ◽  
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.

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