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This seminar, presented by Dr. Michael A. Kalwat of the Indiana Biosciences Research Institute (IBRI) discusses beta-cell dysfunction in diabetes and congenital hyperinsulinism. Dr. Kalwat and his team have identified a small molecule causing beta-cell hypersecretion and determined the compound's target for future therapeutic intervention. Chapters 00:00:00 - 00:01:26 Introduction and Speaker Introduction 00:01:27 - 00:02:44 Overview of Dr. Kalwat's Presentation 00:02:44 - 00:05:12 The Global Diabetes Problem and Beta-Cell Function 00:05:14 - 00:07:56 Beta-Cell Failure in Diabetes and Congenital Hyperinsulinism 00:07:56 - 00:08:44 Insulin Secretion Mechanism 00:08:47 - 00:09:51 Identifying a Small Molecule Causing Insulin Hypersecretion 00:09:51 - 00:11:47 Beta-Cell Line Reporter and Compound Screening 00:11:54 - 00:14:03 Beta-Cell Response to Hypersecretion Compound 00:14:05 - 00:16:03 Drug-Induced Beta-Cell Stress and Mechanisms and Protective Effects of Nifedipine 00:16:08 - 00:17:54 Novel Compound Affects Beta-cell Hypersecretion Stress Response 00:17:55 - 00:20:10 VDAC1 as a Potential Drug Target 00:20:10 - 00:22:18 Validation of VDAC1 as a Target for SW16789 00:22:27 - 00:23:10 Confirmation of Results and Compound Activity 00:23:12 - 00:24:46 Time Course RNA-Seq and Gene Expression Analysis 00:24:47 - 00:27:14 “Hypersecretion Signature” and ER Stress Response 00:27:14 - 00:29:27 ERAD Pathway and Beta-Cell Response to Hypersecretion 00:29:28 - 00:34:10 ERAD Pathway Investigation in Type 2 Diabetes 00:34:10 - 00:36:23 Polyribosomal Fractionation Assay and Protein Translation Analysis 00:36:28 - 00:38:42 Applying Machine Learning to Single-Cell Beta-Cell Data 00:38:43 - 00:40:57 Degas Analysis of Single-Cell Human Islet Data and DLK1 Gene Identification 00:40:57 - 00:43:33 DLK1 Depletion in Type 2 Diabetic Beta-Cells 00:46:51 - 00:54:07 Conclusion and Q&A