Excessive iron accumulation induces beta cell cellular oxidative stress and insulin secretory dysfunction in MIN6 cells

Blesia, V., Patel, V., Al‐Obaidi, H. and Zariwala, M. 2019. Excessive iron accumulation induces beta cell cellular oxidative stress and insulin secretory dysfunction in MIN6 cells. Diabetes UK Professional Conference 2019. Liverpool 06 - 08 Mar 2019 Wiley. doi:10.1111/dme.2_13883

TitleExcessive iron accumulation induces beta cell cellular oxidative stress and insulin secretory dysfunction in MIN6 cells
AuthorsBlesia, V., Patel, V., Al‐Obaidi, H. and Zariwala, M.
TypeConference paper
Abstract

Aims: Exposure to high levels of glucose and iron have been co‐related to reactive oxygen species (ROS) generation and oxidative stress in beta cell. This study aimed to test their accumulation in the beta cell and effects upon cellular oxidative dysfunction, cell viability, and insulin synthesis and secretion.

Methods: MIN6 pseudoislets were exposed to a range of iron concentrations (20–100µM) at predefined glucose levels (5.5 and 11mM) in a static incubation experiment (48 and 72h). Iron storage was assessed by a ferritin immunoassay. Cellular insulin release and content were measured by an insulin immunoassay. ROS mediated cellular oxidative stress was estimated by measuring cellular lipid peroxidation (TBARS assay) and cell viability was assessed by a resazurin dye‐based assay.

Results: Our results demonstrate that the presence of 11mM glucose and 100µM iron exposure at 72h exerted the most detrimental effect on the MIN6 beta cell viability (viability ≤59.5% and ≤54% respectively, n = 4). This observation is consistent with the data from cellular iron uptake analysis, which revealed the highest iron accumulation (ferritin = 325 ± 2.62ng/µg protein, n = 4) and TBARS assay that demonstrated the highest levels of lipid peroxidation (323.9 ± 1.57nmol/µg protein, n = 4) under these conditions. Insulin secretion and content were progressively decreased corresponding to chronic incubation time (27.5 ± 0.4and 38.4 ± 2.83ng/mg protein, respectively, p < 0.05, n = 4).

Summary: Our data suggest that exposure to high iron and glucose concentrations results in cellular damage and may initiate secretory dysfunction in the beta cell.

Year2019
ConferenceDiabetes UK Professional Conference 2019
PublisherWiley
Publication dates
Published05 Mar 2019
JournalDiabetic Medicine
Journal citation36 (S1), pp. 26-46
ISSN0742-3071
Digital Object Identifier (DOI)doi:10.1111/dme.2_13883

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Sugden, M.C., Zariwala, M.G. and Holness, M.J. 2009. PPARs and the orchestration of metabolic fuel selection. Pharmacological Research. 60 (3), p. 141–150. doi:10.1016/j.phrs.2009.03.014

Liver metabolism: biochemical and molecular regulations
Gyamfi, D. and Patel, V. 2009. Liver metabolism: biochemical and molecular regulations. in: Preedy, V.R. (ed.) Nutrition, diet therapy, and the liver London CRC Press. pp. 3-15

Hepatic oxidative stress and apoptosis following acute alcohol
Everitt, H.E., Tewfik, I., Preedy, V.R. and Patel, V. 2009. Hepatic oxidative stress and apoptosis following acute alcohol. Alcohol & Alcoholism. 44, p. p85.

Tomatoes: origin, cultivation techniques, and germplasm resources
da Silva, D.J.H., Abreu, F.B., Caliman, F.R.B., Antonio, A.C. and Patel, V. 2008. Tomatoes: origin, cultivation techniques, and germplasm resources. in: Preedy, V.R. and Watson, R.R. (ed.) Tomatoes and tomato products: nutritional, medicinal and therapeutic properties CRC Press. pp. 3-26

Effects of 4-hydroxynonenal on mitochondrial 3-hydroxy-3methylglutaryl (HMG-CoA) synthase
Patel, V., Spencer, C.H., Young, T.A., Lively, M.O. and Cunningham, C.C. 2007. Effects of 4-hydroxynonenal on mitochondrial 3-hydroxy-3methylglutaryl (HMG-CoA) synthase. Free Radical Biology and Medicine. 43 (11), pp. 1499-1507. doi:10.1016/j.freeradbiomed.2007.08.004

Nutrition and alcoholic liver disease
Everitt, H.E., Patel, V. and Tewfik, I. 2007. Nutrition and alcoholic liver disease. Nutrition Bulletin. 32 (2), pp. 138-144. doi:10.1111/j.1467-3010.2007.00627.x

Prolactin in culture leads to a shift in stimulatory threshold but does not augment the K-ATP channel independent pathway for glucose-stimulated insulin secretion
Zariwala, M., Holness, M.J., Turner, M.D. and Sugden, M.C. 2007. Prolactin in culture leads to a shift in stimulatory threshold but does not augment the K-ATP channel independent pathway for glucose-stimulated insulin secretion. Diabetic Medicine. 24 (S1), p. 33. doi:10.1111/j.1464-5491.2007.02126.x

Enhancement of immune response of HBsAg loaded poly(L-lactic acid) microspheres against Hepatitis B through incorporation of alum and chitosan
Pandit, S., Cevher, E, Zariwala, M., Somavarapu, S. and Alpar, H.O. 2007. Enhancement of immune response of HBsAg loaded poly(L-lactic acid) microspheres against Hepatitis B through incorporation of alum and chitosan. Journal of Microencapsulation. 24 (6), p. 539–552. doi:10.1080/02652040701443700

Diet, obesity and diabetes: a current update
Walker, C.G., Zariwala, M.G., Holness, M.J. and Sugden, M.C. 2007. Diet, obesity and diabetes: a current update. Clinical Science. 112 (2), pp. 93-111. doi:10.1042/CS20060150

Early protein restriction attenuates effects of increased age to suppress the response of adipose-tissue LPL activity to feeding
Zariwala, M., Holness, M.J. and Sugden, M.C. 2006. Early protein restriction attenuates effects of increased age to suppress the response of adipose-tissue LPL activity to feeding. Diabetic Medicine. 23 (S2), pp. 31-138. doi:10.1111/j.1466-5468.2006.01875.x

Protein adduct species in muscle and liver of rats following acute ethanol administration
Patel, V., Worrall, S., Emery, P.W. and Preedy, V.R. 2005. Protein adduct species in muscle and liver of rats following acute ethanol administration. Alcohol & Alcoholism. 40 (6), pp. 485-493. doi:10.1093/alcalc/agh196

Liver dysfunction induced by bile duct ligation and galactosamine injection alters cardiac protein synthesis
Hunter, R.V., Patel, V., Baker, A.J. and Preedy, V.R. 2004. Liver dysfunction induced by bile duct ligation and galactosamine injection alters cardiac protein synthesis. Metabolism: Clinical and Experimental. 53 (8), pp. 964-968. doi:10.1016/j.metabol.2003.11.015

Protein metabolism in alcohol misuse and toxicity
Preedy, V.R., Koll, M., Adachi, J., Mantle, D., Patel, V. and Peters, T. 2003. Protein metabolism in alcohol misuse and toxicity. in: Watson, R.R. and Preedy, V.R. (ed.) Nutrition and alcohol: linking nutrient interactions and dietary intake London CRC Press. pp. 261-300

Chronic ethanol consumption increases the concentration of a 4-hydroxynonenal adduct with the mitochondrial hydroxy methyl glutaryl CoA synthase in liver
Patel, V., Spencer, C. and Cunningham, C.C. 2003. Chronic ethanol consumption increases the concentration of a 4-hydroxynonenal adduct with the mitochondrial hydroxy methyl glutaryl CoA synthase in liver. Hepatology. 38, p. p393.

Emerging techniques in biomedical research and their application to alcohol toxicity
Patel, V., Chaurand, P., Caprioli, R., Austen, B., Frears, E., Manca, F., Davies, H., Vrana, K., Wheeler, M. and Preedy, V.R. 2003. Emerging techniques in biomedical research and their application to alcohol toxicity. Alcoholism: Clinical and Experimental Research. 27 (2), pp. 348-353.

Altered hepatic mitochondrial ribosome structure following chronic ethanol consumption
Patel, V. and Cunningham, C.C. 2002. Altered hepatic mitochondrial ribosome structure following chronic ethanol consumption. Archives of Biochemistry and Biophysics. 398 (1), pp. 41-50. doi:10.1006/abbi.2001.2701

Chronic ethanol consumption increases the formation of an aldehyde-protein adduct in hepatic mitochondria
Patel, V., Young, T.A. and Cunningham, C.C. 2002. Chronic ethanol consumption increases the formation of an aldehyde-protein adduct in hepatic mitochondria. Alcoholism: Clinical and Experimental Research.

Cardioprotective effect of propranolol from alcohol-induced heart muscle damage as assessed by plasma cardiac troponin-T.
Patel, V., Ajmal, R., Sherwood, R., Sullivan, A., Richardson, P. and Preedy, V.R. 2001. Cardioprotective effect of propranolol from alcohol-induced heart muscle damage as assessed by plasma cardiac troponin-T. Alcoholism: Clinical and Experimental Research. 25 (6), pp. 882-889. doi:10.1111/j.1530-0277.2001.tb02294.x

Diarrhea reduces the rates of cardiac protein synthesis in myofibrillar protein fractions in rats in vivo
Hunter, R.V., Patel, V., Miell, J., Wong, H.J., Marway, J., Richardson, P. and Preedy, V.R. 2001. Diarrhea reduces the rates of cardiac protein synthesis in myofibrillar protein fractions in rats in vivo. Journal of Nutrition. 131 (5), pp. 1513-1519.

Acute doxorubicin (adriamycin) dosage does not reduce cardiac protein synthesis in vivo, but decreases diaminopeptidase I and proline endopeptidase activities
Zima, T., Tesar, V., Mantle, D., Koll, M., Patel, V., Richardson, P. and Preedy, V.R. 2001. Acute doxorubicin (adriamycin) dosage does not reduce cardiac protein synthesis in vivo, but decreases diaminopeptidase I and proline endopeptidase activities. Experimental and Molecular Pathology. 70 (2), pp. 154-161. doi:10.1006/exmp.2000.2353

Physiochemical properties of rat liver mitochondrial ribosomes
Patel, V., Cunningham, C.C. and Hantgan, R. 2001. Physiochemical properties of rat liver mitochondrial ribosomes. Journal of Biological Chemistry. 276 (9), pp. 6739-6746. doi:10.1074/jbc.M005781200

In vivo protein synthetic rates of atrial, ventricular, and pulmonary tissue proteins in aortic constriction, goldblatt, and bromoethylamine models of hypertension
Siddiq, T., Patel, V., Sherwood, R., Richardson, P. and Preedy, V.R. 2001. In vivo protein synthetic rates of atrial, ventricular, and pulmonary tissue proteins in aortic constriction, goldblatt, and bromoethylamine models of hypertension. Experimental and Molecular Pathology. 70 (1), pp. 19-30. doi:10.1006/exmp.2000.2333

Ethanol and oxidative stress
Sun, A., Ingelman-Sundberg, M., Neve, E., Matsumoto, H., Nishitani, Y., Minowa, Y., Fukui, Y., Bailey, S., Patel, V., Cunningham, C.C., Zima, T., Fialova, L., Mikulikova, L., Popov, P., Malbohan, I., Janebova, M., Nespor, K. and Sun, G. 2001. Ethanol and oxidative stress. Alcoholism: Clinical and Experimental Research. 25 (5 Suppl.), pp. 237S-243S.

Alpha-Tocopherol supplementation does not prevent acute alcohol-induced heart muscle damage
Koll, M., Patel, V., Sherwood, R.A., Seitz, H.K., Simanowski, U.A., Richardson, P.J., Peters, T.J. and Preedy, V.R. 2001. Alpha-Tocopherol supplementation does not prevent acute alcohol-induced heart muscle damage. Proceedings of the Nutrition Society. 60, p. P125A.

Ethanol and protein metabolism
Cunningham, C.C., Preedy, V.R., Paice, A., Hesketh, J., Peters, T., Patel, V., Volpi, E., Mawatari, K., Masaki, H., Mori, H. and Torii, K. 2001. Ethanol and protein metabolism. Alcoholism: Clinical and Experimental Research. 25 (5 Suppl.), pp. 262S-268S.

Chronic ethanol consumption alters the glutathione/glutathione peroxidase-1 system and protein oxidation status in rat liver
Bailey, S., Patel, V., Young, T.A., Asayama, K. and Cunningham, C.C. 2001. Chronic ethanol consumption alters the glutathione/glutathione peroxidase-1 system and protein oxidation status in rat liver. Alcoholism: Clinical and Experimental Research. 25 (5), pp. 726-733.

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