Unique features of β-cell metabolism are lost in type 2 diabetes
Muñoz, Felipe LU ; Fex, Malin LU ; Moritz, Thomas ; Mulder, Hindrik LU
and Cataldo, Luis Rodrigo
LU
(2024)
In Acta Physiologica
- Abstract
Pancreatic β cells play an essential role in the control of systemic glucose homeostasis as they sense blood glucose levels and respond by secreting insulin. Upon stimulating glucose uptake in insulin-sensitive tissues post-prandially, this anabolic hormone restores blood glucose levels to pre-prandial levels. Maintaining physiological glucose levels thus relies on proper β-cell function. To fulfill this highly specialized nutrient sensor role, β cells have evolved a unique genetic program that shapes its distinct cellular metabolism. In this review, the unique genetic and metabolic features of β cells will be outlined, including their alterations in type 2 diabetes (T2D). β cells selectively express a set of genes in a cell... (More)
Pancreatic β cells play an essential role in the control of systemic glucose homeostasis as they sense blood glucose levels and respond by secreting insulin. Upon stimulating glucose uptake in insulin-sensitive tissues post-prandially, this anabolic hormone restores blood glucose levels to pre-prandial levels. Maintaining physiological glucose levels thus relies on proper β-cell function. To fulfill this highly specialized nutrient sensor role, β cells have evolved a unique genetic program that shapes its distinct cellular metabolism. In this review, the unique genetic and metabolic features of β cells will be outlined, including their alterations in type 2 diabetes (T2D). β cells selectively express a set of genes in a cell type-specific manner; for instance, the glucose activating hexokinase IV enzyme or Glucokinase (GCK), whereas other genes are selectively “disallowed”, including lactate dehydrogenase A (LDHA) and monocarboxylate transporter 1 (MCT1). This selective gene program equips β cells with a unique metabolic apparatus to ensure that nutrient metabolism is coupled to appropriate insulin secretion, thereby avoiding hyperglycemia, as well as life-threatening hypoglycemia. Unlike most cell types, β cells exhibit specialized bioenergetic features, including supply-driven rather than demand-driven metabolism and a high basal mitochondrial proton leak respiration. The understanding of these unique genetically programmed metabolic features and their alterations that lead to β-cell dysfunction is crucial for a comprehensive understanding of T2D pathophysiology and the development of innovative therapeutic approaches for T2D patients.
(Less)
- author
- Muñoz, Felipe
LU
; Fex, Malin
LU
; Moritz, Thomas
; Mulder, Hindrik
LU
and Cataldo, Luis Rodrigo
LU
- organization
- publishing date
- 2024
- type
- Contribution to journal
- publication status
- in press
- subject
- keywords
- disallowed genes, insulin secretion, metabolism, mitochondria, type 2 diabetes, β cells
- in
- Acta Physiologica
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:38656044
- scopus:85191303067
- ISSN
- 1748-1708
- DOI
- 10.1111/apha.14148
- language
- English
- LU publication?
- yes
- id
- 488cff31-d616-4424-8754-07d4b6c4ee7f
- date added to LUP
- 2024-05-06 09:09:33
- date last changed
- 2024-05-20 11:25:00
@article{488cff31-d616-4424-8754-07d4b6c4ee7f,
abstract = {{<p>Pancreatic β cells play an essential role in the control of systemic glucose homeostasis as they sense blood glucose levels and respond by secreting insulin. Upon stimulating glucose uptake in insulin-sensitive tissues post-prandially, this anabolic hormone restores blood glucose levels to pre-prandial levels. Maintaining physiological glucose levels thus relies on proper β-cell function. To fulfill this highly specialized nutrient sensor role, β cells have evolved a unique genetic program that shapes its distinct cellular metabolism. In this review, the unique genetic and metabolic features of β cells will be outlined, including their alterations in type 2 diabetes (T2D). β cells selectively express a set of genes in a cell type-specific manner; for instance, the glucose activating hexokinase IV enzyme or Glucokinase (GCK), whereas other genes are selectively “disallowed”, including lactate dehydrogenase A (LDHA) and monocarboxylate transporter 1 (MCT1). This selective gene program equips β cells with a unique metabolic apparatus to ensure that nutrient metabolism is coupled to appropriate insulin secretion, thereby avoiding hyperglycemia, as well as life-threatening hypoglycemia. Unlike most cell types, β cells exhibit specialized bioenergetic features, including supply-driven rather than demand-driven metabolism and a high basal mitochondrial proton leak respiration. The understanding of these unique genetically programmed metabolic features and their alterations that lead to β-cell dysfunction is crucial for a comprehensive understanding of T2D pathophysiology and the development of innovative therapeutic approaches for T2D patients.</p>}},
author = {{Muñoz, Felipe and Fex, Malin and Moritz, Thomas and Mulder, Hindrik and Cataldo, Luis Rodrigo}},
issn = {{1748-1708}},
keywords = {{disallowed genes; insulin secretion; metabolism; mitochondria; type 2 diabetes; β cells}},
language = {{eng}},
publisher = {{Wiley-Blackwell}},
series = {{Acta Physiologica}},
title = {{Unique features of β-cell metabolism are lost in type 2 diabetes}},
url = {{http://dx.doi.org/10.1111/apha.14148}},
doi = {{10.1111/apha.14148}},
year = {{2024}},
}