Keio University · 의학
요시후미 사이쇼 교수의 연구실은 당뇨병의 병태생리학적 기전과 치료 전략에 중점을 두고 있으며, 특히 췌장의 구조적 변화(췌장량, 지방 축적), β세포 기능 및 질병 진행 메커니즘을 영상학적, 해부학적 접근을 통해 규명하고 있습니다. 고령화와 비만, 제2형 당뇨병이 췌장 구조와 기능에 미치는 영향을 종합적으로 분석하며, 메트포르민의 면역 및 염증 조절 작용 등 약리적 효과에 대해서도 연구하고 있습니다. 환자의 삶의 질을 고려한 치료 평가 방법 개발도 함께 진행하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
Our aims were (1) by computed tomography (CT) to establish a population database for pancreas volume (parenchyma and fat) from birth to age 100 years, (2) in adults, to establish the impact of gender, obesity, and the presence or absence of type-2 diabetes on pancreatic volume (parenchyma and fat), and (3) to confirm the latter histologically from pancreatic tissue obtained at autopsy with a particular emphasis on whether pancreatic fat is increased in type-2 diabetes. We measured pancreas volum
Metformin is an oral hypoglycemic agent which is most widely used as first-line therapy for type 2 diabetes. Metformin improves hyperglycemia by suppressing hepatic glucose production and increasing glucose uptake in muscle. Metformin also has been shown to reduce cardiovascular events in randomized controlled trials; however, the underlying mechanism remains to be established. Recent preclinical and clinical studies have suggested that metformin not only improves chronic inflammation through th
β-Cell mass in human obesity increases by ~50% by an increase in β-cell number, the source of which is unknown. β-Cell mass is well preserved in humans with advanced aging.
Type 2 diabetes (T2DM) is characterized by insulin resistance and β-cell dysfunction. Although, in contrast to type 1 diabetes, insulin resistance is assumed to be a major pathophysiological feature of T2DM, T2DM never develops unless β-cells fail to compensate insulin resistance. Recent studies have revealed that a deficit of β-cell functional mass is an essential component of the pathophysiology of T2DM, implying that β-cell deficit is a common feature of both type 1 and type 2 diabetes. β-cel
Diabetes is associated with a two to three-fold increase in risk of cardiovascular disease. However, intensive glucose-lowering therapy aiming at reducing HbA1c to a near-normal level failed to suppress cardiovascular events in recent randomized controlled trials. HbA1c reflects average glucose level rather than glycemic variability. In in vivo and in vitro studies, glycemic variability has been shown to be associated with greater reactive oxygen species production and vascular damage, compared
The efficacy of diabetes treatment should not be evaluated solely by HbA1c levels as they should also focus on patient-reported outcomes (PROs), such as patient satisfaction, wellbeing and quality of life. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) has been developed to assess patient satisfaction with diabetes treatment. DTSQ has been translated into more than 100 languages and is widely used in many countries, since it is relatively easy to answer and is used for both patients wi
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of oral hypoglycemic agents which increase urinary glucose excretion by suppressing glucose reabsorption at the proximal tubule in the kidney. SGLT2 inhibitors lower glycated hemoglobin (HbA1c) by 0.6-0.8% (6-8 mmol/mol) without increasing the risk of hypoglycemia and induce weight loss and improve various metabolic parameters including blood pressure, lipid profile and hyperuricemia. Recent cardiovascular (CV) outcome trials ha
Type 2 diabetes (T2DM) is characterized by insulin resistance and beta-cell dysfunction. Although insulin resistance is assumed to be a main pathophysiological feature of the development of T2DM, recent studies have revealed that a deficit of functional beta-cell mass is an essential factor for the pathophysiology of T2DM. Pancreatic fat contents increase with obesity and are suggested to cause beta-cell dysfunction. Since the beta-cell dysfunction induced by obesity or progressive decline with
Type 2 diabetes is a progressive disease and most patients with type 2 diabetes eventually need insulin therapy. The objective of this study was to clarify C-peptide immunoreactivity (CPR), a marker of beta cell function, as a predictor of requirement for insulin therapy. We conducted a retrospective study of 579 consecutive subjects with type 2 diabetes who were admitted to our hospital from 2000 to 2007 and were able to be followed up for at least 6 months after discharge. Fasting and postpran
C-peptide is secreted from pancreatic β cells at an equimolar ratio to insulin. Since, in contrast to insulin, C-peptide is not extracted by the liver and other organs, C-peptide reflects endogenous insulin secretion more accurately than insulin. C-peptide is therefore used as a marker of β cell function. C-peptide has been mainly used to assess the presence of an insulin-dependent state for the diagnosis of type 1 diabetes. However, recent studies have revealed that β cell dysfunction is also a
Vesicular monoamine transporter 2 (VMAT2) is expressed in pancreatic beta cells and has recently been proposed as a target for measurement of beta cell mass in vivo. We questioned, (1) What proportion of beta cells express VMAT2? (2) Is VMAT2 expressed by other pancreatic endocrine or non-endocrine cells? (3) Is the relationship between VMAT2 and insulin expression disturbed in type 1 (T1DM) or type 2 diabetes (T2DM)? Human pancreas (7 non-diabetics, 5 T2DM, 10 T1DM) was immunostained for insuli
There was no increase in β-cell mass and no detectable change in β-cell turnover in Japanese obese individuals.
Type 2 diabetes (T2DM) is characterized by insulin resistance and beta cell dysfunction. Recent evidence has emerged that beta cell dysfunction is a common pathogenetic feature of both type 1 and type 2 diabetes, and T2DM never develops without beta cell dysfunction. Therefore, treatment of T2DM should aim to restore beta cell function. Although the treatment of T2DM has greatly improved over the past few decades, remaining issues in the current treatment of T2DM include (1) hypoglycemia; (2) bo
The pancreas is comprised of exocrine and endocrine components. Despite the fact that they are derived from a common origin in utero, these two compartments are often studied individually because of the different roles and functions of the exocrine and endocrine pancreas. Recent studies have shown that not only type 1 diabetes (T1D), but also type 2 diabetes (T2D), is characterized by a deficit in beta-cell mass, suggesting that pathological changes in the pancreas are critical events in the nat
The aim of this study is to explore beta cell dysfunction and its clinical significance in gestational diabetes mellitus (GDM). We assessed insulin sensitivity and insulin secretion in a total of 277 Japanese women between 24 and 27 weeks of pregnancy who underwent a 2 h, 75 g oral glucose tolerance test (OGTT) because of an abnormal result on a 1 h 50 g oral glucose challenge conducted as part of a standard screening for GDM. Insulin sensitivity was evaluated by an insulin sensitivity index der