Apoptosis signal regulating kinase-1 and NADPH oxidase mediate human amylin evoked redox stress and apoptosis in pancreatic beta-cells

Publication date: Available online 6 April 2018Source: Biochimica et Biophysica Acta (BBA) - BiomembranesAuthor(s): Sanghamitra Singh, Diti Chatterjee Bhowmick, Satyabrata Pany, Myungkuk Joe, Noor Zaghlula, Aleksandar M. JeremicAbstractMisfolded toxic human islet amyloid polypeptide or amylin (hA) and plasma membrane-associated redox complex, NADPH oxidase (NOX), have been implicated in the islet β-cell demise associated with type-2 diabetes mellitus (T2DM). Studies show that hA accumulation is stressful to β-cells and that misfolding of human amylin evokes redox stress and activates mitogen activated protein (MAP) kinases, p38 MAPK and c-Jun N-terminal (JNK) kinase. However, the molecular link and causality between hA-evoked redox stress, NOX activity and MAP kinases signaling in pancreatic β-cells is incompletely understood. Here, we show that in the process of activating JNK, aggregation prone hA also activates an upstream apoptosis signal regulating kinase-1 (ASK1) with concomitant decrease in intracellular levels of reduced glutathione. Inhibition of ASK1 kinase activity, either by specific ASK1 inhibitor, NQDI1 or by thiol antioxidants reduces human amylin-evoked ASK1 and JNK activation and consequently human amylin toxicity in rat insulinoma Rin-m5F cells and human islets. β-cell specific overexpression of human amylin in mouse islets elicited ASK1 phosphorylation and activation in β-cells but not in other rodent's islet or exocrine cells. This...
Source: Biochimica et Biophysica Acta (BBA) Biomembranes - Category: Biochemistry Source Type: research

Related Links:

This study suggests a novel regulatory pathway in β-cells involving proteasome, FOXA2, and IAPP, which can be possibly targeted to regulate hIAPP levels and islet amyloidosis in T2DM.
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Protein Synthesis and Degradation Source Type: research
We report a case of a patient with a long history of type 2 diabetes who presented with a subcutaneous mass in the abdomen at a preferred insulin injection site. Examination by light microscopy revealed diffuse deposition of eosinophilic material. Two of the tissue fragments contained numerous 30–40 μm spherical bodies within the eosinophilic material. The bodies had dark centers with peripheral eosinophilic material. Polarized sections stained with Congo red showed apple green birefringence, a characteristic of amyloid. Immunohistochemistry was positive for insulin antibodies in the dark spherules and the surroun...
Source: The American Journal of Dermatopathology - Category: Pathology Tags: Extraordinary Case Report Source Type: research
Publication date: Available online 6 April 2018 Source:Biochimica et Biophysica Acta (BBA) - Biomembranes Author(s): Sanghamitra Singh, Diti Chatterjee Bhowmick, Satyabrata Pany, Myungkuk Joe, Noor Zaghlula, Aleksandar M. Jeremic Misfolded toxic human islet amyloid polypeptide or amylin (hA) and plasma membrane-associated redox complex, NADPH oxidase (NOX), have been implicated in the islet β-cell demise associated with type-2 diabetes mellitus (T2DM). Studies show that hA accumulation is stressful to β-cells and that misfolding of human amylin evokes redox stress and activates mitogen activated protein (MAP) ki...
Source: Biochimica et Biophysica Acta (BBA) Biomembranes - Category: Biochemistry Source Type: research
Abstract Misfolded toxic human islet amyloid polypeptide or amylin (hA) and plasma membrane-associated redox complex, NADPH oxidase (NOX), have been implicated in the islet β-cell demise associated with type-2 diabetes mellitus (T2DM). Studies show that hA accumulation is stressful to β-cells and that misfolding of human amylin evokes redox stress and activates mitogen activated protein (MAP) kinases, p38 MAPK and c-Jun N-terminal (JNK) kinase. However, the molecular link and causality between hA-evoked redox stress, NOX activity and MAP kinases signaling in pancreatic β-cells is incompletely unders...
Source: Biochimica et Biophysica Acta - Category: Biochemistry Authors: Tags: Biochim Biophys Acta Source Type: research
An 82-year-old woman presented to our outpatient clinic with a 6-month history of recurrent internal bleeding near the eyes. The patient had a history of type 2 diabetes mellitus, but had no significant medical history including traumatic injuries. Physical examination revealed bilateral periorbital ecchymosis and large tongue (Figure 1). Serum protein electrophoresis revealed an M-peak in the gamma fraction, and urine immunofixation electrophoresis was positive for Bence-Jones protein. In addition, amyloid fibrils were detected in biopsy of abdominal subcutaneous fat tissue.
Source: The American Journal of Medicine - Category: General Medicine Authors: Tags: Clinical Communication to the Editor Source Type: research
In this study, to examine the relationship between the induction of AA amyloidosis and chromic abnormalities such as autoimmune disease or type 2 diabetes mellitus, amyloid fibrils from mice, cattle, or chickens were experimentally injected into disease model mice. Wild-type mice were used as controls. The concentrations of SAA, IL-6, and IL-10 in autoimmune disease model mice were higher than those of control mice. However, induction of AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice was lower than that in control mice, and the amount of amyloid deposits in the spleens of both mouse models was...
Source: Experimental Animals - Category: Research Tags: Exp Anim Source Type: research
In conclusion, we found that IS status was associated with a significant increase in Hannum DNA methylation, likely as a consequence of the accumulation of cardiovascular risk factors, and near signification with Horvath method. Patients with IS were biologically older than controls, a difference that was more obvious in young stroke. This could open up the possibility of useful new biomarker of stroke risk. Latest Headlines from Fight Aging! A Profile of Kelsey Moody and Ichor Therapeutics https://www.fightaging.org/archives/2016/09/a-profile-of-kelsey-moody
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Amyloidosis is a group of disorders that can manifest in virtually any organ system in the body and is thought to be secondary to misfolding of extracellular proteins with subsequent deposition in tissues. The precursor protein that is produced in excess defines the specific amyloid type. This requires histopathological confirmation using Congo red dye with its characteristic demonstration of green birefringence under cross-polarized light. Gastrointestinal (GI) manifestations are common and the degree of organ involvement dictates the symptoms that a patient will experience. The small intestine usually has the most amyloi...
Source: European Journal of Gastroenterology and Hepatology - Category: Gastroenterology Tags: Review Articles Source Type: research
In this study, to examine the relationship between the induction of AA amyloidosis and chromic abnormalities such as autoimmune disease or type 2 diabetes mellitus, amyloid fibrils from mice, cattle, or chickens were experimentally injected into disease model mice. Wild-type mice were used as controls. The concentrations of SAA, IL-6, and IL-10 in autoimmune disease model mice were higher than those of control mice. However, induction of AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice was lower than that in control mice, and the amount of amyloid deposits in the spleens of both mouse models was...
Source: Experimental Animals - Category: Research Tags: Exp Anim Source Type: research
Authors: Singh S, Trikha S, Bhowmick DC, Sarkar AA, Jeremic AM Abstract Amyloidosis is a biological event in which proteins undergo structural transitions from soluble monomers and oligomers to insoluble fibrillar aggregates that are often toxic to cells. Exactly how amyloid proteins, such as the pancreatic hormone amylin, aggregate and kill cells is still unclear. Islet amyloid polypeptide, or amylin, is a recently discovered hormone that is stored and co-released with insulin from pancreatic islet β-cells. The pathology of type 2 diabetes mellitus (T2DM) is characterized by an excessive extracellular and int...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
More News: Amyloidosis | Biochemistry | Diabetes | Diabetes Mellitus | Diabetes Type 2 | Endocrinology | Pancreas | Study | Toxicology