Our research aims to understand the mechanism behind pancreatic beta cell failure in type 2 diabetes. Although type 2 diabetes is triggered by insulin resistance due to excessive nutrition, the reduction of functional beta cell mass is ultimately responsible for the inability to maintain glucose homeostasis in type 2 diabetes. Thus, the restoration of healthy beta cell mass is an important goal of diabetes therapy and yet has not been achieved in therapeutics available now.
Thelaboratory currently focuses on how lipid droplet proteins optimize intracellular lipid metabolism to support insulin secretion while preventing beta cells from excessive lipid load. The exposure of beta cells to lipids are known to enhance insulin secretion acutely, while the prolonged exposure leads to beta cell dysfunction and apoptosis. We have revealed that lipid droplet protein perilipin 5 plays an important role in supporting insulin secretion through the regulation of intracellular lipid metabolism. The laboratory works on the molecular target by which perilipin 5 augments insulin secretion. In addition, the team has been studying mice deficient of perilipins in beta cells as a model of beta cell dysfunction associated with over–nutrition. Dr. Imai is also extending her work of perilipins to other tissues with active lipid metabolism such as the liver considering that the excessive lipid accumulation in the liver (NAFLD) is closely associated with obesity and diabetes.
An additional area of research interest includes islet inflammation that is also considered to play a role in beta cell loss in type 2 diabetes. Theresearch team has utilized human islets and pancreas from non-diabetic and diabetic organ donors to dissect sequence of events during the progression of beta cell failure in diabetes.
Ultimately, the research team seeks to combine knowledge from key projects to identify a new target to improve beta cell health and function as a treatment for diabetes.
Role of the 12-Lipoxygenase Pathway in Diabetes Pathogenesis and Complications.
Dobrian AD, Morris MA, Taylor-Fishwick DA, Holman TR, Imai Y, Mirmira RG, Nadler JL.
Pharmacol Ther. 2018 Oct 19. pii: S0163-7258(18)30194-3.
Delivery of shRNA via lentivirus in human pseudoislets provides a model to test dynamic regulation of insulin secretion and gene function in human islets.
Harata M, Liu S, Promes JA, Burand AJ, Ankrum JA, Imai Y.
Physiol Rep. 2018 Oct;6(20):e13907
12-Lipoxygenase Inhibitor Improves Functions of Cytokine-Treated Human Islets and Type 2 Diabetic Islets.
Ma K, Xiao A, Park SH, Glenn L, Jackson L, Barot T, Weaver JR, Taylor-Fishwick DA, Luci DK, Maloney DJ, Mirmira RG, Imai Y, Nadler JL. J Clin Endocrinol Metab. 2017 Aug 1;102(8):2789-2797. doi: 10.1210/jc.2017-00267.
Pancreatic islet neuropeptide Y overexpression has minimal effect on islet morphology and β-cell adaptation to high-fat diet.
Machida Y, Bruinsma C, Hallinger DR, Roper SM, Garcia E, Trevino MB, Nadler J, Ahima R, Imai Y.
Endocrinology. 2014 Dec;155(12):4634-40. doi: 10.1210/en.2014-1537. Epub 2014 Oct 6.
Alterations of pancreatic islet structure, metabolism and gene expression in diet-induced obese C57BL/6J mice.
Roat R, Rao V, Doliba NM, Matschinsky FM, Tobias JW, Garcia E, Ahima RS, Imai Y.
PLoS One. 2014 Feb 5;9(2):e86815. doi: 10.1371/journal.pone.0086815. eCollection 2014.
Effects of perilipin 2 antisense oligonucleotide treatment on hepatic lipid metabolism and gene expression.
Imai Y, Boyle S, Varela GM, Caron E, Yin X, Dhir R, Dhir R, Graham MJ, Ahima RS.
Physiol Genomics. 2012 Nov 15;44(22):1125-31. doi: 10.1152/physiolgenomics.00045.2012. Epub 2012 Sep 25.