title: Compensatory hyperinsulinemia in high-fat diet-induced obese mice is associated with enhanced insulin translation in islets.
abstract: A high-fat diet (HF) is associated with obesity, insulin resistance, and hyperglycemia. Animal studies have shown compensatory mechanisms in pancreatic β-cells after high fat load, such as increased pancreatic β-cell mass, enhanced insulin secretion, and exocytosis. However, the effects of high fat intake on insulin synthesis are obscure. Here, we investigated whether insulin synthesis was altered in correlation with an HF diet, for the purpose of obtaining further understanding of the compensatory mechanisms in pancreatic β-cells. Mice fed an HF diet are obese, insulin resistant, hyperinsulinemic, and glucose intolerant. In islets of mice fed an HF diet, more storage of insulin was identified. We analyzed insulin translation in mouse islets, as well as in INS-1 cells, using non-radioisotope chemicals. We found that insulin translational levels were significantly increased in islets of mice fed an HF diet to meet systemic demand, without altering its transcriptional levels. Our data showed that not only increased pancreatic β-cell mass and insulin secretion but also elevated insulin translation is the major compensatory mechanism of pancreatic β-cells.
authors: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: akanno@med.kobe-u.ac.jp.
authors: Ayumi
authors: A
authors: Kanno
authors: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: asahara@med.kobe-u.ac.jp.
authors: Shun-Ichiro
authors: SI
authors: Asahara
authors: Division of Medical Chemistry, Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe 654-0142, Japan. Electronic address: katsuhisa.m.0707@gmail.com.
authors: Katsuhisa
authors: K
authors: Masuda
authors: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: tomokazu@med.kobe-u.ac.jp.
authors: Tomokazu
authors: T
authors: Matsuda
authors: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: koyanagi@med.kobe-u.ac.jp.
authors: Maki
authors: M
authors: Kimura-Koyanagi
authors: Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0047, Japan. Electronic address: seino@med.kobe-u.ac.jp.
authors: Susumu
authors: S
authors: Seino
authors: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: ogawa@med.kobe-u.ac.jp.
authors: Wataru
authors: W
authors: Ogawa
authors: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Division of Medical Chemistry, Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe 654-0142, Japan. Electronic address: kido@med.kobe-u.ac.jp.
authors: Yoshiaki
authors: Y
authors: Kido
mesh_terms: D000818:Animals; D002460:Cell Line; D059305:Diet, High-Fat / Q000009:adverse effects*; D006946:Hyperinsulinism / Q000150:complications* / Q000235:genetics / Q000473:pathology; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000150:complications* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D014176:Protein Biosynthesis; D014158:Transcription, Genetic
chemical_list: D007328:Insulin
keywords: High-fat diet; Insulin translation; Mouse islet