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Article ; Online: Agitated saline test as a simple but reliable method of intraoperative diagnosis and evaluation of unroofed coronary sinus.

Yamamoto, Tomohiro / Yamada, Teppei / Seino, Yutaka / Hayama, Kyo / Shiraishi, Shuichi

JA clinical reports

2024 Volume 10, Issue 1, Page(s) 28

Language	English
Publishing date	2024-04-25
Publishing country	Germany
Document type	Letter
ISSN	2363-9024
ISSN (online)	2363-9024
DOI	10.1186/s40981-024-00709-0
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Article ; Online: Is caloric restriction enough to increase longevity? Fasting and circadian alignment.

Hamamoto, Yoshiyuki / Kurose, Takeshi / Seino, Yutaka

Journal of diabetes investigation

2023 Volume 14, Issue 8, Page(s) 933–935

Abstract: Effects of caloric restriction, fasting and circadian alignment on longevity in mice and potential risks and benefits of extrapolation to humans. ...

Abstract	Effects of caloric restriction, fasting and circadian alignment on longevity in mice and potential risks and benefits of extrapolation to humans.
MeSH term(s)	Humans ; Animals ; Mice ; Longevity ; Caloric Restriction ; Aging ; Fasting
Language	English
Publishing date	2023-06-12
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2625840-7
ISSN	2040-1124 ; 2040-1116
ISSN (online)	2040-1124
ISSN	2040-1116
DOI	10.1111/jdi.14033
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Zs.A 6920: Show issues

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Article ; Online: Long-term safety and efficacy of SGLT2 inhibitor use in older east Asians with type 2 diabetes.

Takahashi, Yoshihiro / Seino, Yutaka / Yabe, Daisuke

Journal of diabetes investigation

2023 Volume 15, Issue 1, Page(s) 63–66

Abstract: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have been shown in cardiovascular outcome trials to reduce the risk of heart failure and major adverse cardiovascular as well as renal events in individuals with type 2 diabetes. Moreover, clinical ... ...

Abstract	Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have been shown in cardiovascular outcome trials to reduce the risk of heart failure and major adverse cardiovascular as well as renal events in individuals with type 2 diabetes. Moreover, clinical evidence indicates that SGLT2i use reduces heart failure and chronic kidney disease (CKD) in east Asian patients with type 2 diabetes. Thus, SGLT2is might seem to be the preferred treatment for older patients with type 2 diabetes even in the presence of multiple comorbidities. However, older patients with type 2 diabetes may well have impaired physiological function, making the risk of certain adverse events higher than that in the general population. While a randomized clinical trial has been conducted to evaluate changes in skeletal muscle mass and function as well as those in cognitive function with SGLT2i use in older Japanese individuals with type 2 diabetes who are otherwise healthy, the safety of SGLT2is remains to be established among older individuals with type 2 diabetes also having impaired activity of daily living and/or cognitive impairment. Even so, international and domestic consensus reports recommend SGLT2is for patients with type 2 diabetes and heart failure, CKD, and/or cardiovascular diseases, and SGLT2is are being widely prescribed by general practitioners to older individuals with type 2 diabetes with little regard to the patient's comorbidities. We maintain that SGLT2i use in older patients with type 2 diabetes should be prescribed cautiously in consideration of the pathophysiology of the disease and the presence of complications and comorbidities as well as the individual's lifestyle.
MeSH term(s)	Aged ; Humans ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/epidemiology ; East Asian People ; Heart Failure/complications ; Hypoglycemic Agents/adverse effects ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/drug therapy ; Sodium-Glucose Transporter 2 Inhibitors/adverse effects
Chemical Substances	Hypoglycemic Agents ; Sodium-Glucose Transporter 2 Inhibitors
Language	English
Publishing date	2023-10-10
Publishing country	Japan
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2625840-7
ISSN	2040-1124 ; 2040-1116
ISSN (online)	2040-1124
ISSN	2040-1116
DOI	10.1111/jdi.14097
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Article ; Online: Identifying nerve to vastus medialis at adductor canal entry.

Watanabe, Tatsunori / Mera, Hisashi / Seino, Yutaka

Journal of anesthesia

2023 Volume 37, Issue 5, Page(s) 813–814

MeSH term(s)	Quadriceps Muscle/innervation ; Thigh/innervation ; Muscle, Skeletal
Language	English
Publishing date	2023-06-26
Publishing country	Japan
Document type	Letter
ZDB-ID	1107821-2
ISSN	1438-8359 ; 0913-8668
ISSN (online)	1438-8359
ISSN	0913-8668
DOI	10.1007/s00540-023-03213-4
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Zs.A 3408: Show issues

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Article ; Online: Luseogliflozin for the treatment of type 2 diabetes.

Seino, Yutaka

Expert opinion on pharmacotherapy

2014 Volume 15, Issue 18, Page(s) 2741–2749

Abstract: Introduction: Sodium glucose cotransporter 2 (SGLT2) inhibitors are expected to provide adequate glycemic control, and be safe and well tolerated, for treating type 2 diabetes mellitus (T2DM). Luseogliflozin is a highly selective SGLT2 inhibitor that ... ...

Abstract	Introduction: Sodium glucose cotransporter 2 (SGLT2) inhibitors are expected to provide adequate glycemic control, and be safe and well tolerated, for treating type 2 diabetes mellitus (T2DM). Luseogliflozin is a highly selective SGLT2 inhibitor that was recently approved for marketing and launched in Japan to treat T2DM. Areas covered: This review summarizes the published data regarding the mechanism of action, clinical efficacy, and safety of luseogliflozin for treating T2DM. Other potential benefits of luseogliflozin, including lowering body weight and blood pressure, beyond its glucose-lowering effects are also discussed. Expert opinion: Luseogliflozin lowers plasma glucose concentration and body weight, and has beneficial effects on other clinically relevant parameters, including blood pressure and uric acid, in patients with T2DM. Although it had a good safety profile in clinical trials, there may be some safety concerns, including a possible decrease in muscle mass and an increase in ketone bodies. Therefore, careful administration and consideration of its benefit-risk balance are necessary. When using luseogliflozin, it is important to select appropriate patients and to adhere to its guidelines for use. If used correctly, luseogliflozin is expected to be positioned as a new type of oral hypoglycemic drug for treating T2DM.
MeSH term(s)	Blood Glucose/analysis ; Clinical Trials as Topic ; Diabetes Mellitus, Type 2/drug therapy ; Drug Therapy, Combination ; Half-Life ; Humans ; Hypoglycemic Agents/chemistry ; Hypoglycemic Agents/pharmacokinetics ; Hypoglycemic Agents/therapeutic use ; Sodium-Glucose Transporter 2/antagonists & inhibitors ; Sodium-Glucose Transporter 2/metabolism ; Sorbitol/analogs & derivatives ; Sorbitol/chemistry ; Sorbitol/pharmacokinetics ; Sorbitol/therapeutic use
Chemical Substances	Blood Glucose ; Hypoglycemic Agents ; Sodium-Glucose Transporter 2 ; Sorbitol (506T60A25R) ; 1,5-anhydro-1-(5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl)-1-thioglucitol (C596HWF74Z)
Language	English
Publishing date	2014-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2001535-5
ISSN	1744-7666 ; 1465-6566
ISSN (online)	1744-7666
ISSN	1465-6566
DOI	10.1517/14656566.2014.978290
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Zs.A 5130: Show issues

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Article ; Online: Efficacy and safety of the sodium-glucose co-transporter-2 inhibitor empagliflozin in elderly Japanese adults (≥65 years) with type 2 diabetes: A randomized, double-blind, placebo-controlled, 52-week clinical trial (EMPA-ELDERLY).

Yabe, Daisuke / Shiki, Kosuke / Homma, Gosuke / Meinicke, Thomas / Ogura, Yuji / Seino, Yutaka

Diabetes, obesity & metabolism

2023 Volume 25, Issue 12, Page(s) 3538–3548

Abstract: Aim: Use of sodium-glucose co-transporter-2 inhibitors (SGLT2is) for glycaemic control is increasing in individuals with type 2 diabetes (T2D) for their additional benefits on heart failure and chronic kidney disease. However, SGLT2is generally reduce ... ...

Abstract	Aim: Use of sodium-glucose co-transporter-2 inhibitors (SGLT2is) for glycaemic control is increasing in individuals with type 2 diabetes (T2D) for their additional benefits on heart failure and chronic kidney disease. However, SGLT2is generally reduce body weight, which might promote sarcopenia in older individuals. We evaluated the effects of the SGLT2i empagliflozin on muscle mass and strength in addition to glucose control in elderly adults with T2D. Materials and methods: Individuals with T2D aged ≥65 years with body mass index ≥22 kg/m Results: Of the 129 individuals randomized, 72.4% were men, mean age 74.1 years, body mass index 25.6 kg/m Conclusions: Empagliflozin improved glucose control and reduced body weight without compromising muscle mass or strength in elderly adults with T2D in this trial.
MeSH term(s)	Aged ; Female ; Humans ; Male ; Benzhydryl Compounds/therapeutic use ; Blood Glucose ; Body Weight ; Diabetes Mellitus, Type 2/drug therapy ; Double-Blind Method ; East Asian People ; Glycated Hemoglobin ; Hypoglycemic Agents/therapeutic use ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Treatment Outcome
Chemical Substances	Benzhydryl Compounds ; Blood Glucose ; empagliflozin (HDC1R2M35U) ; Glycated Hemoglobin ; Hypoglycemic Agents ; Sodium-Glucose Transporter 2 Inhibitors
Language	English
Publishing date	2023-08-25
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1454944-x
ISSN	1463-1326 ; 1462-8902
ISSN (online)	1463-1326
ISSN	1462-8902
DOI	10.1111/dom.15249
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Zs.A 5442: Show issues

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Article ; Online: Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial.

Inagaki, Nobuya / Takeuchi, Masakazu / Oura, Tomonori / Imaoka, Takeshi / Seino, Yutaka

The lancet. Diabetes & endocrinology

2022 Volume 10, Issue 9, Page(s) 623–633

Abstract: Background: As the disease progresses, many patients with type 2 diabetes have difficulty in reaching treatment goals. We aimed to assess the efficacy and safety of tirzepatide, a novel GIP and GLP-1 receptor agonist, compared with dulaglutide in ... ...

Abstract	Background: As the disease progresses, many patients with type 2 diabetes have difficulty in reaching treatment goals. We aimed to assess the efficacy and safety of tirzepatide, a novel GIP and GLP-1 receptor agonist, compared with dulaglutide in Japanese patients with type 2 diabetes. Methods: This multicentre, randomised, double-blind, parallel, active-controlled, phase 3 trial was conducted in 46 medical research centres and hospitals in Japan. Adults aged 20 years or older with type 2 diabetes who had discontinued oral antihyperglycaemic monotherapy or were treatment-naïve were included. Participants were randomly assigned (1:1:1:1) to receive tirzepatide (5, 10, or 15 mg) or dulaglutide (0·75 mg) once per week using a computer-generated random sequence with an Interactive Web Response System. Participants were stratified based on baseline HbA Findings: Between May 7, 2019, and March 31, 2021, 821 participants were assessed for study eligibility and 636 were randomly assigned to receive at least one dose of tirzepatide 5 mg (n=159), 10 mg (n=158), or 15 mg (n=160), or dulaglutide 0·75 mg (n=159). 615 (97%) participants completed the study and 21 (3%) discontinued. Participants had a mean age of 56·6 years (SD 10·3) and were mostly male (481 [76%]). At week 52, HbA Interpretation: Tirzepatide was superior compared with dulaglutide for glycaemic control and reduction in bodyweight. The safety profile of tirzepatide was consistent with that of GLP-1 receptor agonists, indicating a potential therapeutic use in Japanese patients with type 2 diabetes. Funding: Eli Lilly and Company. Translation: For the Japanese translation of the abstract see Supplementary Materials section.
MeSH term(s)	Adult ; Body Weight ; Diabetes Mellitus, Type 2 ; Double-Blind Method ; Female ; Gastric Inhibitory Polypeptide ; Glucagon-Like Peptide-1 Receptor ; Glucagon-Like Peptides/analogs & derivatives ; Glycated Hemoglobin A ; Humans ; Hypoglycemic Agents ; Immunoglobulin Fc Fragments ; Japan ; Male ; Middle Aged ; Recombinant Fusion Proteins ; Treatment Outcome
Chemical Substances	Glucagon-Like Peptide-1 Receptor ; Glycated Hemoglobin A ; Hypoglycemic Agents ; Immunoglobulin Fc Fragments ; Recombinant Fusion Proteins ; Gastric Inhibitory Polypeptide (59392-49-3) ; Glucagon-Like Peptides (62340-29-8) ; tirzepatide (OYN3CCI6QE) ; dulaglutide (WTT295HSY5)
Language	English
Publishing date	2022-07-30
Publishing country	England
Document type	Clinical Trial, Phase III ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ISSN	2213-8595
ISSN (online)	2213-8595
DOI	10.1016/S2213-8587(22)00188-7
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Article: The Insulin Response to Oral Glucose in GIP and GLP-1 Receptor Knockout Mice: Review of the Literature and Stepwise Glucose Dose Response Studies in Female Mice.

Ahrén, Bo / Yamada, Yuichiro / Seino, Yutaka

Frontiers in endocrinology

2021 Volume 12, Page(s) 665537

Abstract: A key factor for the insulin response to oral glucose is the pro-glucagon derived incretin hormone glucagon-like peptide-1 (GLP-1), together with the companion incretin hormone, glucose-dependent insulinotropic polypeptide (GIP). Studies in GIP and GLP-1 ...

Abstract	A key factor for the insulin response to oral glucose is the pro-glucagon derived incretin hormone glucagon-like peptide-1 (GLP-1), together with the companion incretin hormone, glucose-dependent insulinotropic polypeptide (GIP). Studies in GIP and GLP-1 receptor knockout (KO) mice have been undertaken in several studies to examine this role of the incretin hormones. In the present study, we reviewed the literature on glucose and insulin responses to oral glucose in these mice. We found six publications with such studies reporting results of thirteen separate study arms. The results were not straightforward, since glucose intolerance in GIP or GLP-1 receptor KO mice were reported only in eight of the arms, whereas normal glucose tolerance was reported in five arms. A general potential weakness of the published study is that each of them have examined effects of only one single dose of glucose. In a previous study in mice with genetic deletion of both GLP-1 and GIP receptors we showed that these mice have impaired insulin response to oral glucose after large but not small glucose loads, suggesting that the relevance of the incretin hormones may be dependent on the glucose load. To further test this hypothesis, we have now performed a stepwise glucose administration through a gastric tube (from zero to 125mg) in model experiments in anesthetized female wildtype, GLP-1 receptor KO and GIP receptor KO mice. We show that GIP receptor KO mice exhibit glucose intolerance in the presence of impaired insulin response after 100 and 125 mg glucose, but not after lower doses of glucose. In contrast, GLP-1 receptor KO mice have normal glucose tolerance after all glucose loads, in the presence of a compensatory increase in the insulin response. Therefore, based on these results and the literature survey, we suggest that GIP and GLP-1 receptor KO mice retain normal glucose tolerance after oral glucose, except after large glucose loads in GIP receptor KO mice, and we also show an adaptive mechanism in GLP-1 receptor KO mice, which needs to be further examined.
MeSH term(s)	Administration, Oral ; Animals ; Female ; Gastric Inhibitory Polypeptide/metabolism ; Glucagon/metabolism ; Glucagon-Like Peptide 1/metabolism ; Glucagon-Like Peptide-1 Receptor/physiology ; Glucose/administration & dosage ; Hypoglycemic Agents/pharmacology ; Insulin/pharmacology ; Insulin Secretion ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/metabolism ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Gastrointestinal Hormone/physiology ; Mice
Chemical Substances	Glucagon-Like Peptide-1 Receptor ; Hypoglycemic Agents ; Insulin ; Receptors, Gastrointestinal Hormone ; Gastric Inhibitory Polypeptide (59392-49-3) ; Glucagon-Like Peptide 1 (89750-14-1) ; Glucagon (9007-92-5) ; gastric inhibitory polypeptide receptor (D6H00MV7K8) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2021-05-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2021.665537
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Article: The mediation by GLP-1 receptors of glucagon-induced insulin secretion revisited in GLP-1 receptor knockout mice

Ahrén, Bo / Yamada, Yuichiro / Seino, Yutaka

Peptides. 2021 Jan., v. 135

2021

Abstract: To study whether activation of GLP-1 receptors importantly contributes to the insulinotropic action of exogenously administered glucagon, we have performed whole animal experiments in normal mice and in mice with GLP-1 receptor knockout. Glucagon (1, 3 ... ...

Abstract	To study whether activation of GLP-1 receptors importantly contributes to the insulinotropic action of exogenously administered glucagon, we have performed whole animal experiments in normal mice and in mice with GLP-1 receptor knockout. Glucagon (1, 3 or 10 μg/kg), the GLP-1 receptor antagonist exendin 9-39 (30 nmol/kg), glucose (0.35 g/kg) or the incretin hormone glucose-dependent insulinotropic polypeptide (GIP; 3 nmol/kg) was injected intravenously or glucose (75 mg) was given orally through gavage. Furthermore, islets were isolated and incubated in the presence of glucose with or without glucagon. It was found that the insulin response to intravenous glucagon was preserved in GLP-1 receptor knockout mice but that glucagon-induced insulin secretion was markedly suppressed in islets from GLP-1 receptor knockout mice. Similarly, the GLP-1 receptor antagonist markedly suppressed glucagon-induced insulin secretion in wildtype mice. These data suggest that GLP-1 receptors contribute to the insulinotropic action of glucagon and that there is a compensatory mechanism in GLP-1 receptor knockout mice that counteracts a reduced effect of glucagon. Two potential compensatory mechanisms (glucose and GIP) were explored. However, neither of these seemed to explain why the insulin response to glucagon is not suppressed in GLP-1 receptor knockout mice. Based on these data we confirm the hypothesis that glucagon-induced insulin secretion is partially mediated by GLP-1 receptors on the beta cells and we propose that a compensatory mechanism, the nature of which remains to be established, is induced in GLP-1 receptor knockout mice to counteract the expected impaired insulin response to glucagon in these mice.
Keywords	antagonists ; gastric inhibitory polypeptide ; glucagon ; glucagon-like peptide 1 ; glucose ; insulin ; insulin secretion ; intravenous injection ; secretin
Language	English
Dates of publication	2021-01
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	769028-9
ISSN	1873-5169 ; 0196-9781
ISSN (online)	1873-5169
ISSN	0196-9781
DOI	10.1016/j.peptides.2020.170434
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 1649: Show issues

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Article: d-Allulose Inhibits Ghrelin-Responsive, Glucose-Sensitive and Neuropeptide Y Neurons in the Arcuate Nucleus and Central Injection Suppresses Appetite-Associated Food Intake in Mice

Rakhat, Yermek / Kaneko, Kentaro / Wang, Lei / Han, Wanxin / Seino, Yutaka / Yabe, Daisuke / Yada, Toshihiko

Nutrients. 2022 July 29, v. 14, no. 15

2022

Abstract: d-allulose, a rare sugar, has sweetness with few calories. d-allulose regulates feeding and glycemia, and ameliorates hyperphagia, obesity and diabetes. All these functions involve the central nervous system. However, central mechanisms underlying these ... ...

Abstract	d-allulose, a rare sugar, has sweetness with few calories. d-allulose regulates feeding and glycemia, and ameliorates hyperphagia, obesity and diabetes. All these functions involve the central nervous system. However, central mechanisms underlying these effects of d-allulose remain unknown. We recently reported that d-allulose activates the anorexigenic neurons in the hypothalamic arcuate nucleus (ARC), the neurons that respond to glucagon-like peptide-1 and that express proopiomelanocortin. However, its action on the orexigenic neurons remains unknown. This study investigated the effects of d-allulose on the ARC neurons implicated in hunger, by measuring cytosolic Ca²⁺ concentration ([Ca²⁺]ᵢ) in single neurons. d-allulose depressed the increases in [Ca²⁺]ᵢ induced by ghrelin and by low glucose in ARC neurons and inhibited spontaneous oscillatory [Ca²⁺]ᵢ increases in neuropeptide Y (NPY) neurons. d-allulose inhibited 10 of 35 (28%) ghrelin-responsive, 18 of 60 (30%) glucose-sensitive and 3 of 8 (37.5%) NPY neurons in ARC. Intracerebroventricular injection of d-allulose inhibited food intake at 20:00 and 22:00, the early dark phase when hunger is promoted. These results indicate that d-allulose suppresses hunger-associated feeding and inhibits hunger-promoting neurons in ARC. These central actions of d-allulose represent the potential of d-allulose to inhibit the hyperphagia with excessive appetite, thereby counteracting obesity and diabetes.
Keywords	blood glucose ; calcium ; central nervous system ; diabetes ; food intake ; ghrelin ; glucagon-like peptide 1 ; glucose ; hunger ; neuropeptide Y ; obesity ; overeating ; pro-opiomelanocortin ; psicose ; sweetness
Language	English
Dates of publication	2022-0729
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2518386-2
ISSN	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14153117
Database	NAL-Catalogue (AGRICOLA)

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