Physiological and pathophysilogical roles of acinar-like cell cluster touching Langerhans islet with thin interstitial surrounding (ATLANTIS) on regeneration and maintenance of beta cell.

• Project/Area Number: 15K09406
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Okinaka Memorial Institute for Medical Research
• Principal Investigator: Kobayashi Tetsuro (財)冲中記念成人病研究所, その他部局等, 研究員 (30113442)
• Co-Investigator(Kenkyū-buntansha): 永淵 正法 佐賀大学, 医学部, 客員研究員 (00150441) ; 雨宮 三千代 (財)冲中記念成人病研究所, その他部局等, 研究員 (00288101) ; 會田 薫 山梨大学, 大学院総合研究部, 医学研究員 (50184015)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 糖尿病 / ウイルス / 再生医学 / EMCウイルス / REGIα / BrdU / インスリン / REGⅠα

Outline of Final Research Achievements

We examined 1) the presence or absence of acinar-like cell clusters touching Langerhans islets with thin interstitial surrounding (ATLANTIS) in homozygous Reg I deficient (Reg I-/-) and wild-type mice, and 2) the possible role of ATLANTIS in the regeneration of beta cell clusters after encephalomyocarditis (EMC) virus (D-variant) infection in Reg I-/- and wild-type mice. ATLANTIS was found in both wild-type and Reg I-/- mice. At 12 days after EMC virus infection, lower BrdU labeling indices were observed in islet beta cells of Reg I-/- mice compared to wild-type mice. Beta cell volume 12 days after EMC virus infection in Reg I-/- mice did not differ from that of wild-type mice.
These results suggest that Reg I, which is released from ATLANTIS to islet beta cell clusters, has a crucial role in beta cell regeneration in EMC virus-induced diabetes. The presence of mechanism(s) other than that mediated by Reg I in beta cell restoration after destruction by EMC virus was also suggested.

Research Products

• [Journal Article] Possible Long-Term Efficacy of Sitagliptin, a Dipeptidyl Peptidase-4 Inhibitor, for Slowly Progressive Type 1 Diabetes (SPIDDM) in the Stage of Non-Insulin-Dependency: An Open-Label Randomized Controlled Pilot Trial (SPAN-S) (2017)
  • Author(s): Awata Takuya、Shimada Akira、Maruyama Taro、Oikawa Yoichi、Yasukawa Nobuyuki、Kurihara Susumu、Miyashita Yumi、Hatano Masako、Ikegami Yuichi、Matsuda Masafumi、Niwa Masataka、Kazama Youichiro、Tanaka Shoichiro、Kobayashi Tetsuro
  • Journal Title: Diabetes Therapy Volume: 8 Issue: 5 Pages: 1123-1134
  • DOI: 10.1007/s13300-017-0299-7
• [Journal Article] Pancreatic ductal hyperplasia/dysplasia with obstructive chronic pancreatitis: an association with reduced pancreatic weight in type 1 diabetes. (2016)
  • Author(s): Kobayashi T, Aida K, Fukui T, Jimbo E, Shimada A, Mori Y, Fujii T, Yagihashi S.
  • Journal Title: Diabetologia Volume: 59 Issue: 4 Pages: 865-867
  • DOI: 10.1007/s00125-016-3867-x
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Predictive value of titer of GAD antibodies for further progression of beta cell dysfunction in slowly progressive insulin-dependent (type 1) diabetes (SPIDDM). (2016)
  • Author(s): Tanaka S, Okubo M, Nagasawa K, Takizawa S, Ichijo M, Ichijo S, Kaneshige M, Aida K, Shimura H, Mori Y, Kobayashi T.
  • Journal Title: Diabetol Int Volume: 7 Issue: 1 Pages: 42-52
  • DOI: 10.1007/s13340-015-0211-5
  • NAID: 40020774251
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Diagnostic criteria for slowly progressive insulin-dependent (type 1) diabetes ellitus (SPIDDM) (2012): report by the Committee on Slowly Progressive Insulin-Dependent (Type 1) Diabetes Mellitus of the Japan Diabetes Society. (2015)
  • Author(s): Tanaka S, Ohmori M, Awata T, Simada A, Mrrao S, Maruyama T, Kamoi K, Kawasaki E, Nakanishi K, Nagata M, Fujii S, Ikegami H, Imagawa A, Uchigata Y, Okubo M, Osawa H, Kajio H, Kawaguchi A, Kawabata Y, Satoh J, Shimizu I, Takahashi K, Makino H, Iwahashi H, Mirra J, Yasuda K, Hanafusa T, Kobayashi T
  • Journal Title: Diabetol Int Volume: 6 Issue: 1 Pages: 1-7
  • DOI: 10.1007/s13340-014-0199-2
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Increased numbers of CD68+ cells of the exocrine pancreas in slowly progressive type 1 diabetes. (2017)
  • Author(s): Fukui T, Kobayshi T, Jimbo E, Aida K, Yagihashi S, Shimada A.
  • Organizer: 15th of International Congress of Immunology of Diabetes Society
  • Int'l Joint Research
• [Presentation] Distinct inflamed changes of the pancreases of slowly progressive insulin-dependent (type 1) diabetes: comparative analysis with enterovirus-nduced fulminant type 1 diabetes. (2017)
  • Author(s): Jimbo E, Kobayashi T, Fukui T, Aida K, Yagihashi S, Shimada A.
  • Organizer: 15th of International Congress of Immunology of Diabetes Society
  • Int'l Joint Research
• [Presentation] 1型糖尿病update 2017 緩徐進行1型糖尿病の成因～膵炎と膵島炎の関係に注目して～。 (2017)
  • Author(s): 福井智康、小林哲郎、八木橋操六
  • Organizer: 第60回糖尿病学会年次学術集会 シンポジウム
• [Presentation] 緩徐進行1型糖尿病の膵外分泌腺の病理学的検討。 (2017)
  • Author(s): 福井智康、小林哲郎、神保江莉加、島田朗、八木橋操六、会田薫
  • Organizer: 第60回糖尿病学会年次学術集会
• [Presentation] 1型糖尿病と腎疾患 2016年6月17-19日 横浜 (2016)
  • Author(s): 小林哲郎
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-06-17
  • Invited
• [Presentation] 1型糖尿病の成因と治療】緩徐進行１型糖尿病の成因に関する最新の知見―膵外分泌腺、膵管異常に注目して― (2016)
  • Author(s): 福井智康、会田薫、神保江莉加、島田朗、八木橋操六、小林哲郎
  • Organizer: 第59回日本糖尿病学会年次学術集会 （シンポジウム）
  • Place of Presentation: 京都
  • Year and Date: 2016-05-19
• [Presentation] 緩徐進行1型糖尿病(SPIDDM)の病理学的検討 (2016)
  • Author(s): 神保江莉加、会田薫、福井智康、八木橋操六、島田朗、小林哲郎
  • Organizer: 第59回日本糖尿病学会年次学術集会
  • Place of Presentation: 京都
  • Year and Date: 2016-05-19
• [Presentation] １型糖尿病のすべて 緩徐進行１型糖尿病の膵病変 (2015)
  • Author(s): 小林哲郎、会田薫、西田頼子、島田朗、八木橋操六、粟田卓也
  • Organizer: 第５８回日本糖尿病年次学術総会
  • Place of Presentation: 海峡メッセ下関
  • Year and Date: 2015-05-21
• [Book] 内分泌・糖尿病・代謝内科 (2017)
  • Author(s): 小林哲郎
  • Total Pages: 7
  • Publisher: 科学評論社