Sasaki, Hironobu

写真a

Affiliation

School of Medicine, Center for Preventive Medicine (Shinanomachi)

Position

Project Assistant Professor (Non-tenured)/Project Research Associate (Non-tenured)/Project Instructor (Non-tenured)

Academic Background 【 Display / hide

  • 2007.04
    -
    2013.03

    Keio University

    University, Graduated

  • 2017.04
    -
    2021.03

    Keio University

    Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

  • Bachelor of Medicine, Keio University, 2013.03

  • Doctor of Medicine, Keio University, Coursework, 2021.03

    Associations of birthweight and history of childhood obesity with beta cell mass in Japanese adults

Licenses and Qualifications 【 Display / hide

  • Board Certified Member of the Japanese Society of Internal Medicine, 2016.09

  • the Japan Medical Association (JMA)-certified Sports Medicine Physician, 2017.03

  • the Japan Medical Association (JMA)-certified Occupational Physician, 2019.07

  • Fellow of the Japan Diabetes Society, 2019.11

  • Diabetologist certified by the Japan Association for Diabetes Education and Care, 2019.12

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Research Areas 【 Display / hide

  • Metabolomics (human islet research)

Research Keywords 【 Display / hide

  • Diabetes

 

Papers 【 Display / hide

  • Revisiting regulators of human β-cell mass to achieve β-cell-centric approach toward type 2 diabetes

    Sasaki H, Saisho Y, Inaishi J, Itoh H

    Journal of the Endocrine Society (Oxford University Press)  5 ( 10 ) bvab128 2021.10

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    <title>Abstract</title>
    Type 2 diabetes (T2DM) is characterized by insulin resistance and β-cell dysfunction. Since patients with T2DM have inadequate β-cell mass (BCM), and β-cell dysfunction worsens glycemic control and makes treatment difficult, therapeutic strategies to preserve and restore BCM are needed.In rodent models, obesity increases BCM about 3-fold, but the increase in BCM in humans is limited. Besides, obesity-induced changes in BCM may show racial differences between East Asians and Caucasians. Recently, the Developmental Origins of Health and Disease hypothesis, which states that the risk of developing non-communicable diseases including T2DM is influenced by the fetal environment, has been proposed. It is known in rodents that animals with low birthweight have reduced BCM through epigenetic modifications, making them more susceptible to diabetes in the future. Similarly, in humans, we revealed that individuals born with low birthweight have lower BCM in adulthood. Since β-cell replication is more frequently observed in the five years after birth, and β-cells are found to be more plastic in that period, a history of childhood obesity increases BCM. BCM in patients with T2DM is reduced by 20-65% compared with that in individuals without T2DM. However, since BCM starts to decrease from the stage of borderline diabetes, early intervention is essential for β-cell protection. In this review, we summarize the current knowledge on regulatory factors of human β-cell mass in health and diabetes, and propose the β-cell centric concept of diabetes to enhance a more pathophysiology-based treatment approach for T2DM.

  • Reduced beta cell number rather than size is a major contributor to beta cell loss in type 2 diabetes

    Sasaki H, Saisho Y, Inaishi J, Watanabe Y, Tsuchiya T, Makio M, Sato M, Nishikawa M, Kitago M, Yamada T, Itoh H

    Diabetologia (Springer)  64 ( 8 ) 1816 - 1821 2021.08

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0012186X

     View Summary

    Aims/hypothesis: Type 2 diabetes is characterised by reduced beta cell mass (BCM). However, it remains uncertain whether the reduction in BCM in type 2 diabetes is due to a decrease in size or number of beta cells. Our aim was to examine the impact of beta cell size and number on islet morphology in humans with and without type 2 diabetes. Methods: Pancreas samples were obtained from 64 Japanese adults with (n = 26) and without (n = 38) type 2 diabetes who underwent pancreatectomy. Using pancreatic tissues stained for insulin, we estimated beta cell size based on beta cell diameter. Beta cell number was estimated from the product of fractional beta cell area and pancreas volume divided by beta cell size. The associations of beta cell size and number with islet morphology and metabolic status were examined. Results: Both beta cell size (548.7 ± 58.5 vs 606.7 ± 65.0 μm , p < 0.01) and number (5.10 × 10 ± 2.35 × 10 vs 8.16 × 10 ± 4.27 × 10 , p < 0.01) were decreased in participants with type 2 diabetes compared with those without diabetes, with the relative reduction in beta cell number (37%) being greater than for beta cell size (10%). Beta cell number but not size was positively correlated with BCM in participants with and without type 2 diabetes (r = 0.97 and r = 0.98, both p < 0.01) and negatively correlated with HbA (r = −0.45, p < 0.01). Conclusions/interpretation: Both beta cell size and number were reduced in participants with type 2 diabetes, with the relative reduction in beta cell number being greater. Decrease in beta cell number appears to be a major contributor to reduced BCM in type 2 diabetes. Graphical abstract: [Figure not available: see fulltext.] 3 8 8 8 8 1c

  • Associations of birthweight and history of childhood obesity with beta cell mass in Japanese adults

    Sasaki H, Saisho Y, Inaishi J, Watanabe Y, Tsuchiya T, Makio M, Sato M, Kitago M, Yamada T, Itoh H

    Diabetologia (Springer)  63 ( 6 ) 1199 - 1210 2020.06

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0012186X

     View Summary

    Aims/hypothesis: Low birthweight is associated with a high risk of diabetes, but there are no reports discussing birthweight and pancreatic tissues in humans. The purpose of this study was to examine the correlation between birthweight and beta and alpha cell mass in humans. Methods: Sixty-four Japanese adults with and without diabetes who underwent pancreatectomy and were able to recall their weight history including birthweight were included. Pancreatic tissues were stained for insulin and glucagon, and fractional beta cell area (BCA) and alpha cell area (ACA) were quantified. Islet size and density and beta cell replication were also quantified and their associations with birthweight were evaluated. Results: In participants without diabetes, there was a weak positive correlation between birthweight and BCA (R = 0.34, p = 0.03). The group with a history of childhood obesity, but not the group with a history of obesity in adulthood only, showed higher BCA compared with those without a history of obesity (1.78 ± 0.74% vs 0.99 ± 0.53%, p = 0.01), and the correlation coefficient between birthweight and BCA increased after excluding those with a history of childhood obesity (R = 0.51, p < 0.01). In those with diabetes, there was no correlation between birthweight and BCA. No correlation was found between birthweight and ACA in either those with or without diabetes. Conclusions/interpretation: Birthweight and beta, but not alpha, cell mass are positively correlated in non-diabetic adults, and a history of childhood obesity may affect beta cell mass. [Figure not available: see fulltext.].

  • Efficacy and safety of once-weekly exenatide after switching from twice-daily exenatide in patients with type 2 diabetes

    Watanabe Y, Saisho Y, Inaishi J, Kou K, Yamauchi A, Kanazawa Y, Okubo Y, Tokui M, Imai T, Murakami R, Tsuchiya T, Sasaki H, Masaoka T, Irie J, Meguro S, Itoh H

    Journal of Diabetes Investigation (John Wiley & Sons)  11 ( 2 ) 382 - 388 2020.03

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  20401116

     View Summary

    Aims/Introduction: To evaluate the efficacy and safety of once-weekly (q.w.) extended-release exenatide after switching from twice-daily (b.i.d.) exenatide in patients with type 2 diabetes. Materials and Methods: This was an investigator-initiated, prospective, single-arm, multicenter study. Individuals with type 2 diabetes who had been treated with exenatide b.i.d. for at least 3 months were enrolled and switched to exenatide q.w. for 24 weeks. The primary end-point was change in HbA1c at week 24 to test the glucose-lowering effect of exenatide q.w. versus exenatide b.i.d. Results: A total of 58 Japanese individuals with type 2 diabetes completed the study. Glycated hemoglobin was reduced by 0.2% at week 24 (7.2 ± 1.2% vs 7.0 ± 1.2% [56 ± 13 vs 53 ± 13 mmol/mol], 95% confidence interval −0.4 to −0.03%, P < 0.005 for non-inferiority, P = 0.01 for superiority). Fasting plasma glucose was reduced by 12 mg/dL at week 24 (154 ± 46 vs 142 ± 46 mg/dL, P = 0.02). β-Cell function assessed by homeostasis model assessment of β-cell function and C-peptide index was significantly improved at week 24. The incidence of self-reported hypoglycemia was reduced, and treatment satisfaction assessed by the Diabetes Treatment Satisfaction Questionnaire and Diabetes Medication Satisfaction Questionnaire was improved at week 24, with no change in body weight. There was no serious adverse event related to the study drug. Conclusions: Switching from exenatide b.i.d. to exenatide q.w. resulted in a reduction in glycated hemoglobin, fasting plasma glucose and the incidence of hypoglycemia, and improvement in β-cell function and treatment satisfaction in patients with type 2 diabetes. These findings will be useful for selecting optimal treatment in individuals with type 2 diabetes.

Awards 【 Display / hide

  • Medical Research Encouragement Prize

    2021.12, Tokyo Medical Association

    Type of Award: Awards of Publisher, Newspaper Company and Foundation

  • Young Investigator Award

    2021.06, the Japan Diabetes Society

    Type of Award: Awards of National Conference, Council and Symposium

  • Clinical Investigator Award

    2020.10, the Hormone Station of Japan

    Type of Award: Awards of Publisher, Newspaper Company and Foundation

 

Committee Experiences 【 Display / hide

  • 2020
    -
    Present

    Reviewer Board Member of the Japanese Society of Internal Medicine