Featured
-
-
Article
| Open AccessIlluminating the complete ß-cell mass of the human pancreas- signifying a new view on the islets of Langerhans
The pancreatic islets of Langerhans play a pivotal role in regulating blood glucose homeostasis through the regulated secretion of the hormones insulin and glucagon. Here, the authors use deep tissue 3D imaging to re-construct the entire human pancreas at microscopic resolution and display previously unrecognized heterogeneities in the islet’s cellularity with pre-clinical and clinical implications.
- Joakim Lehrstrand
- , Wayne I. L. Davies
- & Ulf Ahlgren
-
Article
| Open AccessA human antibody against pathologic IAPP aggregates protects beta cells in type 2 diabetes models
β-cell dysfunction in type 2 diabetes is associated with pathological aggregates of IAPP that accumulate in pancreatic islets. Here, the authors describe a novel antibody cloned from healthy elderly donors that selectively targets IAPP oligomers and protects from IAPP toxicity.
- Fabian Wirth
- , Fabrice D. Heitz
- & Jan Grimm
-
Article
| Open AccessPancreatic Ppy-expressing γ-cells display mixed phenotypic traits and the adaptive plasticity to engage insulin production
The cellular identity and function of the pancreatic polypeptide (Ppy)-producing γ-cells are incompletely understood. Here the authors show that these cells are heterogeneous and display adaptive plasticity to engage in insulin production following β-cell injury, but loss of the Ppy gene or γ-cells in mice does not affect weight or glycemia under basal conditions.
- Marta Perez-Frances
- , Léon van Gurp
- & Pedro L. Herrera
-
Article
| Open AccessDeficiency of PRKD2 triggers hyperinsulinemia and metabolic disorders
Hyperinsulinemia can precede the development of insulin resistance. Here the authors identify a PKD2 mutation that leads to hyperinsulinemia and insulin resistance in Rhesus monkey and show that PKD2 deficiency promotes beta cell insulin secretion by activating L-type Ca2+ channels.
- Yao Xiao
- , Can Wang
- & Xiuqin Zhang
-
Article
| Open AccessLRRC8/VRAC anion channels enhance β-cell glucose sensing and insulin secretion
Insulin secretion by β-cells is stimulated by glucose and is dependent on the induction of β-cell membrane depolarization, mainly driven by the closure of KATP channels, which in turn promotes voltage-gated Ca2+ channel opening. Here the authors show that LRRC8 volume-regulated anion channels (VRACs) modulate glucose-stimulated calcium increase and insulin secretion.
- Till Stuhlmann
- , Rosa Planells-Cases
- & Thomas J. Jentsch
-
Article
| Open AccessLRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus
Type 1 diabetes mellitus (T1DM) is characterized by beta cell loss because of an autoimmune attack. Here the authors show that an agonist for LRH-1/NR5A2, a nuclear receptor known to be protective against beta cell apoptosis, inhibits immune-mediated inflammation and hyperglycemia in T1DM mouse models.
- Nadia Cobo-Vuilleumier
- , Petra I. Lorenzo
- & Benoit R. Gauthier
-
Article
| Open Accessα-cell glucokinase suppresses glucose-regulated glucagon secretion
Glucagon secretion is promoted during hypoglycemia and inhibited by increased glucose levels. Here, Basco et al. show that glucokinase suppresses glucose-regulated glucagon secretion by modulating the intracellular ATP/ADP ratio and the closure of KATP channels in α-cells.
- Davide Basco
- , Quan Zhang
- & Bernard Thorens
-
Article
| Open AccessReplication confers β cell immaturity
Adult beta cells, which are highly specialised insulin-secreting cells, rarely replicate. Puri et al. demonstrate that beta cell proliferative capacity is inversely correlated with their functionality and differentiation state, by inducing proliferation of adult cells with ectopic overexpression of the cell cycle regulator c-Myc.
- Sapna Puri
- , Nilotpal Roy
- & Matthias Hebrok
-
Article
| Open AccessROCKII inhibition promotes the maturation of human pancreatic beta-like cells
Our incomplete understanding of how pancreatic beta cells form limits the generation of beta-like cells from human pluripotent stem cells (hPSC). Here, the authors identify a ROCKII inhibitor H1152 as increasing insulin secreting cells from hPSCs and improving beta-cell maturation on transplantation in vivo.
- Zaniar Ghazizadeh
- , Der-I Kao
- & Shuibing Chen
-
Article
| Open AccessLoss of mTORC1 signalling impairs β-cell homeostasis and insulin processing
Deregulation of mTORC1 pathway has been associated with several human diseases including diabetes, neurodegeneration and cancer. Here Blandino-Rosanoet al. show that mTORC1 signalling controls insulin secretion and β-cell maintenance by regulation of β-cell proliferation, apoptosis and autophagy and insulin processing.
- Manuel Blandino-Rosano
- , Rebecca Barbaresso
- & Ernesto Bernal-Mizrachi
-
Article
| Open AccessSox5 regulates beta-cell phenotype and is reduced in type 2 diabetes
Type 2 diabetes (T2D) is a heterogeneous disorder characterized by insulin resistance and impaired insulin secretion. Here Axelssonet al. show that Sox5, which is reduced in diabetes, regulates a set of differentially expressed genes in T2D and its genetic and pharmacological induction improves insulin secretion by diabetic islets.
- A. S. Axelsson
- , T. Mahdi
- & A. H. Rosengren
-
Article
| Open Accessβ-arrestin-2 is an essential regulator of pancreatic β-cell function under physiological and pathophysiological conditions
Beta-arrestins have key roles in development and metabolic functions as euglycaemic control and insulin sentitivity. Here Zhuet al. show that beta-arrestin-2 regulates insulin secretion and glucose tolerance in mice by promoting CAMKII functions in beta cells.
- Lu Zhu
- , Joana Almaça
- & Jürgen Wess
-
Article
| Open AccessHyperglycaemia induces metabolic dysfunction and glycogen accumulation in pancreatic β-cells
Diabetes is characterized by prolonged hyperglycaemia and tissue damage in pancreatic islets. Here, Brereton et al. show that chronic high glucose levels lead to glycogen accumulation in β-cells, associated with reduced autophagy, impaired metabolism, insulin granule depletion and apoptosis.
- Melissa F. Brereton
- , Maria Rohm
- & Frances M. Ashcroft
-
Article
| Open AccessReversible changes in pancreatic islet structure and function produced by elevated blood glucose
In patients with diabetes, insulin release from pancreatic β-cells is reduced due to altered islet structure and function. Here, Brereton et al. show that elevated blood glucose underlies these changes and is sufficient to reversibly alter β-cell identity in a mouse model of β-cell dysfunction.
- Melissa F. Brereton
- , Michaela Iberl
- & Frances M. Ashcroft
-
Article |
Gap junction signalling is a stress-regulated component of adrenal neuroendocrine stimulus-secretion coupling in vivo
Findings from ex vivo studies suggest that gap junctional coupling contributes to hormone release in neuroendocrine/endocrine tissues. Here, the authors provide in vivo evidence that direct communication between adrenal chromaffin cells viagap junctions contributes to catecholamine secretion.
- Michel G. Desarménien
- , Carole Jourdan
- & Nathalie C. Guérineau
-
Article |
Constitutively active Foxo3 in oocytes preserves ovarian reserve in mice
The number of primordial follicles, which constitute the ovarian reserve, decreases with age. By overexpressing a constitutively active version of the transcription factor FOXO3, the authors increase the ovarian reserve and fertility in aging female mice.
- Emanuele Pelosi
- , Shakib Omari
- & Chris Ottolenghi
-
Article |
A peptide derived from laminin-γ3 reversibly impairs spermatogenesis in rats
The temporal opening and closing of cell–cell junctions at the blood–testis barrier allows the passage of immature germ cells during spermatogenesis. Su and colleagues identify a peptide fragment of the laminin-γ3 chain that disrupts the blood–testis barrier and reversibly impairs spermatogenesis in rats.
- Linlin Su
- , Dolores D. Mruk
- & C. Yan Cheng