PKA. gastric inhibitory polypeptide(gip) glucagonlike peptide-1(glp-1) 2 GIP. Ca 2+ PKA PKA PKA AKAPs(A-kinase anchoring proteins) PKA PKA GLP-1 GLP-1

Transcript

1

2 gastric inhibitory polypeptide(gip) glucagonlike peptide-1(glp-1)2 GIP GLP-1 GLP-1 DPP-4 30 GIP GIP cdna(takeda J. Proc Natl Acad Sci USA 84:7005-8, 1987) (Inagaki N. Mol. Endocrinol. 3: , 1989) GIP cdna (Yasuda K. Biochem. Biophys. Res. Commun. 205: , 1994) (Miyawaki K. Proc. Natl. Acad. Sci. USA. 96: , 1999) GLP-1 camp PKA Epac2 camp Epac2 Rap1 PKA SUR1 VDCC Ca 2+ PKA PKA PKA AKAPs(A-kinase anchoring proteins) PKA PKA APKAs 70 AKAPs PKA 2 2 I II 2 PKA I(PKA-RI) GLP-1 (Song WJ. Cell Metabolism 13:308-19, 2011)AKAPs PKA II(PKA-RII) SPHKAP(SPHK1 interactor, AKAP contain -ing domain) PKA-RI AKAP SPHKAP PKA PKA 70 AKAPs PKA-RI

3 SPHKAP camp/pka PKA-RI SPHKAP PKA (1) SPHKAP 70 AKAPs SPHKAP AKAKs primary islets INS-1 RIN-5 AKAPs quantitative real time PCR SPHKAP SPHKAP primary islets SPHKAP SPHKAP (2) SPHKAP PKA (3) SPHKAP SPHKAP primary islets SPHKAP INS-1 RIN-5 sirna RNA ( -4) SPHKAP -4 mirna SPHKAP SPHKAP INS-1D -4 (4) SPHKAP SPHKAP 1700 PKA AKAPs SPHKAP Sphingosine kinase type 1(SPHK-1) SPHKAP SPHKAP Yeast two-hybrid SPHKAP (1) SPHKAP qrt-pcr INS-1D SPHKAP (1) SPHKAP SPHKAP (2)

4 SPHKAP (3) SPHKAP (4) (3) SPHKAP SPHKAP INS-1D SPHKAP 50% -4 60%(6) INS-1D RNA SPHKAP (7) SPHKAP (2) SPHKAP PKA SPHKAP HEK293 INS-1D SPHKAP PKA-RI (5) PKA-RII SPHKAP PKA-RI SPHKAP -4

5 (4) SPHKAP SPHKAP SPHKAP SPHKAP SPHKAP Yeast two-hybrid SPHKAP 1) Yamamoto T, Horiuchi T, Miyahara H, Yashizawa S, Maehara J, Shono E, Takamura K, Tsujioka K, Kaneko T, Uemura N, Suzawa K, Inagaki N, Umegaki N, Kasamatsu Y, Arinobu Y, Inoue Y, Niiro H, Kashiwagi Y, Harashima S, Tahira T, Tsukamoto H, Akashi K. Hereditary angioedema in Japan: Genetic analysis of 13 unrelated cases. Am J Med Sci 2012;343(3) ) Yamane S, Harada N, Hamasaki A, Muraoka A, Joo E, Suzuki K, Nasteska D, Tanaka S, Ogura M, Harashima S, Inagaki N. Effect of glucose and meal ingestion on incretin secretion in Japanese subjects with normal glucose tolerance. J Diabetes Invest 2012;3(1): ) Harashima S, Ogura M, Tanaka D, Fukushima T, Wang Y, Koizumi T, Aono M, Murata Y, Seike M, Inagaki N. Sitagliptin add-on to low dosage sulphonylureas: efficacy and safety of combination therapy on glycaemic control and insulin secretion capacity in type 2 diabetes. Int J Clin Pract. 2012;66(5): ) Harashima S, Tanaka D, Yamane S, Ogura M, Fujita Y, Murata Y, Seike M, Koizumi T, Aono M, Wang Y, Inagaki N. Efficacy and safety of switching from basal insulin to sitagliptin in Japanese type 2 diabetes patients. Horm Metab Res. 2013;45(3): ) Harashima S, Fukushima T, Sasaki M, Nishi Y, Fujimoto S, Ogura M, Yamane S, Tanaka D, Harada N, Hamasaki A, Nagashima K, Nakahigashi Y, Seino Y, Inagaki N. Self-monitoring of blood glucose (SMBG) improves glycemic control in oral hypoglycemic agents (OHA)-treated type 2 diabetes (SMBG-OHA Study). Diabetes Metab Res Rev. 2013;29(1): ) Hosokawa M, Hamasaki A, Nagashima K, Harashima S, Toyoda K, Fujita Y, Harada N, Nakahigashi Y, Fujimoto S, Inagaki N. Lack of goal attainment regarding the low-density lipoprotein cholesterol level in the management of type 2 diabetes mellitus. Intern Med. 2013;52(21): ) Nishimura A, Harashima S, Honda I, Shimizu Y, Harada N, Nagashima K, Hamasaki A, Hosoda K,Inagaki N. Color record in self-monitoring of blood glucose improves glycemic control by better self-management. Diabetes Technol Ther. 2014;16(7): ) Harashima SI, Nishimura A, Osugi T, Wang Y, Liu Y, Takayama H, Inagaki N. Restless legs syndrome in patients with type 2 diabetes: effectiveness of pramipexole therapy. BMJ Support Palliat Care ) Ikeda K, Fujimoto S, Morling B, Ayano-Takahara S, Carroll AE, Harashima S, Uchida Y, Inagaki N. Social orientation

6 and diabetes-related distress in Japanese and American patients with type 2 diabetes. PLoS One. 2014;9(10):e ) Ayano-Takahara S, Ikeda K, Fujimoto S, Hamasaki A, Harashima S, Toyoda K, Fujita Y, Nagashima K, Tanaka D, Inagaki N. Glycemic variability is associated with quality of life and treatment satisfaction in patients with type 1 diabetes. Diabetes Care. 2015;38(1):e1-2. 1) Wang, Y., Harashima, S., Yamane, S., Inagaki, N. SKIP Inhibits Glucose-Stimulated and Incretin- enhanced Insulin Secretion. 9th International Diabetes Federation Western Pacific Region Congress / 4th Scientific Meeting of the Asian Association for the Study of Diabetes. 2012/11/25, Kyoto Japan. 2) Y. Wang, S. Harashima, S. Yamane, K. Suzuki, N. Harada, N. Inagaki. SKIP inhibits glucose-stimulated and incretin-enhanced insulin secretion. Pancreatic β-cell ~Mini-Symposium~. 2013/1/18, Shiga, Japan. 3). SKIP /5/16, 4) /5/26,. 5) Y, Wang, S.-I. Harashima, S. Yamane, K. Suzuki, N. Harada, Y.-Y. Liu, N. Inagaki. Sphingosine kinase 1 interacting protein (SKIP) inhibits insulin secretion from beta cells through regulation of protein kinase A activity. 49th EASD Annual Meeting, Barcelona. Sep 26, 2013, Barcelona, Spain. 6) Y. Wang, S. Harashima, Y. Liu, S. Yamane, K. Suzuki, N. Harada, N. Inagaki. Sphingosine kinase 1 interacting protein (SKIP) inhibits insulin secretion from beta cells through regulation of protein kinase A activity. 5th Asian Association of the Study for Diabetes. 2013/11/7, Seoul, Korea. 7) D. Tanaka, K. Nagashima, S. Harashima, N. Inagaki. Whole exome sequencing in a Japanese family with highly aggregated type 2 diabetes. 5th Asian Association of the Study for Diabetes. 2013/11/8, Seoul, Korea. 1. Prog Med 2012;32: ;63: ;49; α 2013;4653: αdpp-4 GLP ;4653: α 2013;4653: Medical Practice 2013;30(5): Clinical Study 2013;34(7); Q&ADPP ;96(6); ;6(2); html (1) HARASHIMA, shinichi