Category: Beta Cell Physiology and Dysfunction

Almost 20% of the chromosomal regions associated with the risk of developing of Type 1 diabetes (T1D) identified to date,have no identified candidate causal gene. Often, this is because the genes in those regions have no known roles in the immune system, reflecting the classical view that T1D is caused by the autoimmune destruction of […]

Beta cell dysfunction occurs in the early stages of type 1 (T1D) and type 2 diabetes (T2D) development. Strategies to improve outcomes for the mounting number of diabetic patients requires understanding the complex programs that coordinate a proper insulin release in response to changing blood glucose levels and how these mechanisms falter in diabetogenic settings. […]

Alterations in metabolism are known to play profound roles inthe health ofindividuals with type 1 diabetes (T1D). These alterations lead to disruptions in cell structure, signaling, and energy homeostasis. While most studies focus on identifying genetic or protein signatures of disease, the metabolic profile is a far more dynamic, sensitive, and rapidly-responding molecular measure of […]

There is increasing evidence for cross-talk between the islet and exocrine compartments of the pancreas. Diabetes is a risk factor for exocrine atrophy, pancreatitis, and pancreatic cancer. Conversely, pancreatitis is a risk factor for diabetes. Until now our ability to study human endocrine and exocrine cells has been limited to isolated islets and isolated exocrine […]

ORIGINAL: Type 1 diabetes (T1D) is an autoimmune disease in which clinical symptoms arise as a result of insulin deficiency. While genetic and environmental factors contribute to the disease, in recent years it has become increasingly evident that beta cells might be contributing to their own destruction and might have an active role in type […]

Oxidative stress occurs when increased production of cellular oxidants (e.g. Reactive Oxygen Species, or ROS) is not compensated  for  by  an  increase  in  cellular  antioxidants/antioxidant  enzymes.   A  considerable body  of  evidence  supports  the  conclusion  that  oxidative  stress  is  a common  feature  of type  1 diabetes (T1D), and that the process of autophagy plays a key […]

Our lab has been focusing for many years on the intrinsic stress experienced by pancreatic islet β-cells, which (even in healthy states) live under a strict metabolic mandate to continuously produce and secrete insulin at intensely high rates that predispose these professional secretory cells to secretory exhaustion. β-cells evolved a high-capacity endoplasmic reticulum (ER) organelle […]

The objective of this application is to determine the cellular distribution of Golli protein in human pancreatic islets. Golli (gene expressed in oligodendrocyte lineage) is an alternatively spliced product of myelin basic protein (MBP) gene featured by the presence of a unique Golli domain which contains a 133-amino-acid sequence fused in the N-terminal of classic […]

Emerging evidence suggests beta cell dysfunction and failure precede autoimmune destruction during the development of type 1 diabetes, but the underlying mechanisms are not known. Defining and targeting the changes leading to impaired beta cell function may lead to clinical improvement and prolonged honeymoon period. We have recently discovered that in type 2 diabetes, beta […]

We previously identified the Rab1A small GTPase as a conserved activator of mTORC1 in response to amino acid (AA) stimulation in yeast and mammalian cells. To better understand the physiological function of Rab1A- mTORC1 signaling in vivo, we genetically engineered conditional Rab1A knockout (Rab1A-KO) in mice. We found that tamoxifen-induced Rab1A knockout in young adult […]

Diabetes mellitus is a complex and multifactorial disease characterized by progressive loss or dysfunction of the insulin-producing beta cells in the pancreas. This results in chronic hyperglycemia and systemic metabolic complications and, in the long-term, in multi-organ damages; together, these complications create enormous medical and social burdens as well as causing premature deaths. Today, over […]