Little is known about how T cell pathogenesis is modulated in the islets during T1D, yet this is a critical obstacle for preventing destruction of remaining islets or beta cell grafts. Therefore, we must elucidate mechanisms that promote and prevent the pathogenic autoimmune response in the islets. Our data in the NOD mouse model show […]
Category: Current nPOD Projects
ORIGINAL: Growth and Development of the Endocrine Pancreas in Humans: Extrapolating Normal Physiology to the Regenerative Capacity of the Endocrine Compartment in Type 1 and Type 2 Diabetes; ADDENDUM: The Role of Neuropeptide Y (NPY) in Human Beta Cell Maturation and Diabetes Pathogenesis
ORIGINAL: Chromogranin A is a global marker of endocrine cells. Most endocrine cells in the pancreas, in addition to Chromogranin A, also express other hormones, Insulin and Glucagon being most frequent, with Pancreatic Polypeptide, Somatostatin and Ghrelin in smaller numbers of endocrine cells. We have found that in adult human pancreas a small number of […]
Pancreatic antibacterial responses in T1D
The etiology of autoimmune diabetes is not known. However, the disease is accompanied by varying amounts of immune activation and inflammation. Although genetics clearly plays a role in determining who gets the disease, we do not know the instigating events. There has been a lot of investigation into the potential role of virus infections in […]
Diabetes Virus Detection Study (DiViD)
The Diabetes Virus Detection Study (DiViD) is the first to examine fresh pancreatic tissue at the diagnosis of type 1 diabetes (T1D) for the presence of viruses. Surgical minimal pancreatic tail resection was performed in general anesthesia 3-9 weeks after onset of type 1 diabetes in six adult patients (age 24-35 years). Pancreatic tissues were […]
Immunoregulation of type 1 diabetes
Type 1 Diabetes (T1D) is a disease that results from the autoimmune destruction of insulin-producing beta cells in the pancreas. The current treatment for T1D does not cure the disease or prevent the possibility of other serious complications. The mechanism that leads to the loss of immune tolerance still remains unclear; scientists believe that both […]
NKG2D ligand expression in type 1 diabetes development
Recent evidence derived from animal models of type 1 diabetes indicates that interaction of immune cells expressing the protein known as NKG2D with cells expressing other proteins, termed NKG2D ligands, plays an essential role in initiating diabetes development. In an effort to define more precisely the role these proteins play in type 1 diabetes progression, […]
Role of environmental chemicals in the development of type 1 diabetes
There is a well-documented rise in the incidence of type 1 diabetes (T1D) in industrialized countries suggesting a role for environmental chemical exposures. Alarmingly, the increased incidence is seen mostly in children under age 5. However, research on environmental chemical exposures and T1D is very limited and there is an urgent need for research to […]
Detection of coxsackievirus infection in β-cells in T1D by short fluorescently labeled oligonucleotide probes
Type 1 diabetes (T1D) results from a complex interplay between genetic polymorphisms, immune system and environment. Viruses, mainly enteroviruses such as members of the Coxsackie B virus (CVB) family, have been suspected since long time to trigger diabetes and epidemiological studies support a causative role of viral infections during diabetes onset. Nonetheless, the presence of […]
Origin of composite islet structure in humans
In the adult human pancreas the majority of islets have a clear non-random organization of mantle of non beta cells around beta cell cores, with larger islets usually having multiple such subunits (composite) whereas smaller islets resembled the classic rodent pattern. There is far more variability in islet composition both within each human pancreas and […]
Beta-cell mass in Antibody-positive non-diabetic subjects
The question of the B-cell mass of non-diabetic autoantibody-positive (Ab+) subjects is crucial to understand both common forms of type 1 diabetes and latent autoimmune diabetes (LADA). It is well established that the presence of GAD Abs is not sufficient to predict diabetes or insulin dependency. Knowing the B cell mass of Ab+ donors could […]
Beta cell polarity
Insulin secretion is principally regulated by the beta cell response to glucose. This secretory response is multiphasic with an initial burst of insulin secretion followed by sustained or increasing secretion. This complex timing of secretion is important for body function and is lost in type 2 diabetes. Beta cells normally function, and are normally regulated, […]
Epigenetic analysis of nPOD islet cells
Type 1 Diabetes (T1D) is a complex autoimmune disease affecting more than 30 million people worldwide. T1D is caused by a combination of genetic and epigenetic factors leading to immune destruction of insulin-secreting islet cells. Although significant progress has recently been made in elucidating the genetics of T1D, the non-genetics component has remained poorly defined. […]
Analysis of type 1 interferon responses to rotavirus in patients with type 1 diabetes
Rotavirus infection of children at-risk of type 1 diabetes is associated with disease progression. Similarly, infection of adult non-obese diabetic (NOD) mice with Rhesus monkey rotavirus RRV accelerates diabetes onset. This acceleration correlates with RRV spread to the mesenteric and pancreatic lymph nodes, where virus associates with and activates dendritic cells and induces B and […]