P. Arvan

Small molecule FICD inhibitors suppress endogenous and pathologic FICD-mediated protein AMPylation

This study identifies two small molecule inhibitors of FICD that suppress both endogenous and pathologic protein AMPylation, improving proinsulin processing in β cells.

Permanent Neonatal diabetes-causing Insulin mutations have dominant negative effects on beta cell identity

This study investigates two INS mutations causing permanent neonatal diabetes, showing they impair beta cell function through misfolded proinsulin, ER stress, and dedifferentiation.

Differential roles of beta-cell IP3R and RyR ER Ca2+ channels in ER stress-induced alterations of beta-cell Ca2+ homeostasis

This study investigates how ER stress affects IP3R and RyR Ca2+ channels in beta cells, showing RyR1 dysfunction contributes to Ca2+ dysregulation and apoptosis.

Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues

This study shows that mitochondrial dysfunction triggers a retrograde signaling program that reduces cellular maturity in metabolic tissues, and blocking this signaling can restore cell identity and improve hyperglycemia.

Restoration of PITPNA in Type 2 diabetic human islets reverses pancreatic beta-cell dysfunction

The paper shows restoring PITPNA in T2D human islets reverses beta-cell dysfunction by improving insulin granule maturation and glucose-stimulated insulin secretion.

SERCA2 regulates proinsulin processing and processing enzyme maturation in the pancreatic β cell

This study identifies SERCA2 as a regulator of proinsulin processing and processing enzyme maturation in pancreatic β cells, linking ER Ca2+ levels to impaired glucose tolerance in diabetes.

Inflammatory cytokines rewire the proinsulin interaction network in human islets

This study identifies how inflammatory cytokines alter the proinsulin interactome in human islets, revealing new interactions and mechanisms involved in diabetes-related proinsulin dysregulation.

Age of diabetes onset in the mutant proinsulin syndrome correlates with mutational impairment of protein foldability and stability

The paper investigates how mutations at position B18 in proinsulin affect protein foldability and stability, correlating these effects with the age of diabetes onset in mutant proinsulin syndrome.

Predisposition to Proinsulin Misfolding as a Genetic Risk to Diet-Induced Diabetes

This study shows that a proinsulin mutation increases susceptibility to diet-induced diabetes in mice, with severity linked to genetic dosage and beta-cell dysfunction.

Distinct states of proinsulin misfolding in MIDY

The paper investigates proinsulin misfolding in MIDY mutants, showing that disrupting the Cys(A6)-Cys(A11) bond can restore proper folding and ER export in some mutants.

In vivo imaging of individual islets across the mouse pancreas reveals a heterogeneous insulin secretion response to glucose

The paper uses in vivo imaging to study insulin secretion from individual pancreatic islets in mice, finding that their responses to glucose are heterogeneous in vivo, unlike in culture.

The type 2 diabetes gene product STARD10 is a phosphoinositide binding protein that controls insulin secretory granule biogenesis

This study identifies STARD10 as a phosphoinositide binding protein that regulates insulin granule biogenesis in beta-cells by affecting phosphatidylinositol levels and proinsulin processing.

Establishing cell-intrinsic limitations in cell cycle progression controls graft growth and promotes differentiation of pancreatic endocrine cells

The paper investigates how limitations in S-phase progression affect pancreatic endocrine differentiation and graft growth, finding that impaired DNA replication enhances differentiation and prevents cystic growth.

A reference map of the human proinsulin biosynthetic interaction network

This study identifies a conserved proinsulin interactome in human islets, revealing PRDX4's role in proinsulin folding and its inactivation in T2D.

Role of Proinsulin Self-Association in Mutant INS gene-induced Diabetes of Youth

This study identifies proinsulin self-association as a mechanism driving dominant-negative effects of misfolded proinsulin in MIDY, offering a therapeutic target for enhancing insulin production.

Abnormalities in Proinsulin Processing in Islets from Individuals with Longstanding T1D

The paper investigates proinsulin processing abnormalities in T1D islets, finding reduced processing enzymes and cytokine-induced expression changes.

Discovery of a redox-thiol switch regulating cellular energy metabolism

The paper identifies a Redox Thiol Switch (RTSGS) that regulates cellular energy metabolism by switching between S-glutathionylation and S-sulfhydration, with PCK2 as a novel target.

Preservation of circadian rhythms by the protein folding chaperone, BiP

The paper shows that BiP and chemical chaperones strengthen circadian rhythms in fibroblasts under ER stress and prevent ER stress in tendon by regulating collagen synthesis.