Protective effects of pioglitazone and/or liraglutide on pancreatic β-cells in db/db mice: Comparison of their effects between in an early and advanced stage of diabetes

Tomohiko Kimura; Hideaki Kaneto; Masashi Shimoda; Hidenori Hirukawa; Seizo Okauchi; Kenji Kohara; Sumiko Hamamoto; Kazuhito Tawaramoto; Mitsuru Hashiramoto; Kohei Kaku

doi:10.1016/j.mce.2014.11.018

Protective effects of pioglitazone and/or liraglutide on pancreatic β-cells in db/db mice: Comparison of their effects between in an early and advanced stage of diabetes

Mol Cell Endocrinol. 2015 Jan 15:400:78-89. doi: 10.1016/j.mce.2014.11.018. Epub 2014 Nov 24.

Affiliations

¹ Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki-city, Okayama 701-0192, Japan. Electronic address: tomohiko@med.kawasaki-m.ac.jp.
² Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki-city, Okayama 701-0192, Japan.
³ Division of Diabetes and Endocrinology, Yodogawa Christian Hospital, 1-7-50 Shibajima, Osaka-city, Osaka 533-0024, Japan.
⁴ Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki-city, Okayama 701-0192, Japan; Department of General Internal Medicine 1, Kawasaki Hospital, Kawasaki Medical School, 2-1-80 Nakasange, Okayama-city, Okayama 700-8505, Japan.

PMID: 25463759
DOI: 10.1016/j.mce.2014.11.018

Abstract

The aim was to compare the protective effects of pioglitazone (PIO) and/or liraglutide (LIRA) on β-cells with the progression of diabetes. Male db/db mice were treated with PIO and/or LIRA for 2 weeks in an early and advanced stage. In an early stage insulin biosynthesis and secretion were markedly increased by PIO and LIRA which was not observed in an advanced stage. In concomitant with such phenomena, expression levels of various β-cell-related factors were up-regulated by PIO and LIRA only in an early stage. Furthermore, β-cell mass was also increased by the treatment only in an early stage. Although there was no difference in apoptosis ratio between the two stages, β-cell proliferation was augmented by the treatment only in an early stage. In conclusion, protective effects of pioglitazone and/or liraglutide on β-cells were more powerful in an early stage of diabetes compared to an advanced stage.

Keywords: Cellular kinetics; Liraglutide; Pioglitazone; Progression of diabetic morbidity; β-Cell.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Blood Glucose / metabolism
Caspases / genetics
Caspases / metabolism
Cell Proliferation / drug effects
Diabetes Mellitus, Type 2 / drug therapy*
Diabetes Mellitus, Type 2 / genetics
Diabetes Mellitus, Type 2 / metabolism
Diabetes Mellitus, Type 2 / pathology
Disease Models, Animal
Disease Progression
Gene Expression / drug effects
Glucagon / blood
Glucagon-Like Peptide 1 / analogs & derivatives*
Glucagon-Like Peptide 1 / pharmacology
Hypoglycemic Agents / pharmacology*
Insulin / blood
Insulin-Secreting Cells / drug effects*
Insulin-Secreting Cells / metabolism
Insulin-Secreting Cells / pathology
Ki-67 Antigen / genetics
Ki-67 Antigen / metabolism
Liraglutide
Male
Mice
Mice, Transgenic
Organ Size / drug effects
Pioglitazone
Proto-Oncogene Proteins c-bcl-2 / genetics
Proto-Oncogene Proteins c-bcl-2 / metabolism
RNA, Ribosomal, 18S / genetics
RNA, Ribosomal, 18S / metabolism
Thiazolidinediones / pharmacology*
Time Factors
Triglycerides / blood

Substances

Blood Glucose
Hypoglycemic Agents
Insulin
Ki-67 Antigen
Proto-Oncogene Proteins c-bcl-2
RNA, Ribosomal, 18S
Thiazolidinediones
Triglycerides
Bcl2 protein, mouse
Liraglutide
Glucagon-Like Peptide 1
Glucagon
Caspases
Pioglitazone