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mTORC1 signaling and diabetic kidney disease. mTORC1 信号传导与糖尿病肾病。
IF 1.3 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-06-20 eCollection Date: 2024-10-01 DOI: 10.1007/s13340-024-00738-1
Vinamra Swaroop, Eden Ozkan, Lydia Herrmann, Aaron Thurman, Olivia Kopasz-Gemmen, Abhiram Kunamneni, Ken Inoki

Diabetic kidney disease (DKD) represents the most lethal complication in both type 1 and type 2 diabetes. The disease progresses without obvious symptoms and is often refractory when apparent symptoms have emerged. Although the molecular mechanisms underlying the onset/progression of DKD have been extensively studied, only a few effective therapies are currently available. Pathogenesis of DKD involves multifaced events caused by diabetes, which include alterations of metabolisms, signals, and hemodynamics. While the considerable efficacy of sodium/glucose cotransporter-2 (SGLT2) inhibitors or angiotensin II receptor blockers (ARBs) for DKD has been recognized, the ever-increasing number of patients with diabetes and DKD warrants additional practical therapeutic approaches that prevent DKD from diabetes. One plausible but promising target is the mechanistic target of the rapamycin complex 1 (mTORC1) signaling pathway, which senses cellular nutrients to control various anabolic and catabolic processes. This review introduces the current understanding of the mTOR signaling pathway and its roles in the development of DKD and other chronic kidney diseases (CKDs), and discusses potential therapeutic approaches targeting this pathway for the future treatment of DKD.

糖尿病肾病(DKD)是 1 型和 2 型糖尿病最致命的并发症。这种疾病在没有明显症状的情况下发展,而且在出现明显症状时往往是难治性的。尽管对 DKD 发病/进展的分子机制进行了广泛研究,但目前只有少数几种有效疗法。DKD 的发病机制涉及糖尿病引起的多方面事件,包括代谢、信号和血液动力学的改变。虽然钠/葡萄糖共转运体-2(SGLT2)抑制剂或血管紧张素 II 受体阻滞剂(ARB)对 DKD 的疗效已得到认可,但糖尿病和 DKD 患者人数的不断增加需要更多实用的治疗方法,以防止 DKD 从糖尿病发展为 DKD。雷帕霉素复合体 1(mTORC1)信号通路是一个看似合理但很有前景的靶点,它能感知细胞营养物质,控制各种合成代谢和分解代谢过程。这篇综述介绍了目前对mTOR信号通路的理解及其在DKD和其他慢性肾脏疾病(CKD)发展过程中的作用,并讨论了针对这一通路的潜在治疗方法,以便在未来治疗DKD。
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引用次数: 0
Advances in glucagon research ~ 100th anniversary: invitation to the new 'glucagon-ology'. 胰高血糖素研究进展 ~ 100 周年:新 "胰高血糖素学 "邀请函。
IF 1.3 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-31 eCollection Date: 2024-07-01 DOI: 10.1007/s13340-024-00728-3
Dan Kawamori
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引用次数: 0
Case of new-onset fulminant type 1 diabetes mellitus accompanied by autoimmune thyroid disease after SARS-CoV-2 infection. 感染SARS-CoV-2后新发暴发性1型糖尿病并伴有自身免疫性甲状腺疾病的病例。
IF 1.3 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-30 eCollection Date: 2024-07-01 DOI: 10.1007/s13340-024-00729-2
Keisuke Murakawa, Hiroaki Aasi, Kanako Sato, Saori Yoshioka, Hiroyuki Sho, Ryoko Inui, Motohiro Kosugi, Yoji Hazama, Tetsuyuki Yasuda

There is growing evidence suggesting an association between severe acute respiratory coronavirus syndrome coronavirus 2 (SARS-CoV-2) infection and various extrapulmonary diseases since the advent of coronavirus disease 2019 (COVID-19) pandemic. However, case reports of fulminant type 1 diabetes mellitus (FT1D) following SARS-CoV-2 infection are limited. We encountered a 44-year-old Japanese woman who developed FT1D accompanied by subclinical thyrotoxicosis caused by autoimmune thyroid disease (AITD) approximately one week after SARS-CoV-2 infection. The patient developed fever and flu-like symptom 4 days before transportation and tested positive then for the SARS-CoV-2 antigen self-test. She subsequently developed sudden thirst, polyuria, and fatigue of 1 day duration and was urgently brought to our emergency room. Laboratory findings indicated diabetic ketoacidosis (DKA) without marked elevation of serum glycated hemoglobin (HbA1c) levels (glucose, 930 mg/dL; HbA1c, 7.4%). Her insulin secretory capacity was almost completely depleted, and islet-specific autoantibodies were negative. Endocrine examinations revealed subclinical thyrotoxicosis, which was positive for thyroid stimulation hormone receptor antibodies. Based on these results, the patient was diagnosed with FT1D accompanied by AITD and immediately started on intensive insulin therapy with a basal-bolus subcutaneous insulin regimen. Human leukocyte antigen analysis revealed haplotypes, indicating susceptibility to both FT1D and AITD. Further studies are required to elucidate the causal relationship between SARS-CoV-2 infection, FT1D, and AITD. However, clinicians must be vigilant about possible development of FT1D and AITD to enable accurate diagnosis and treatment of patients with DKA during the COVID-19 pandemic.

自 2019 年冠状病毒病(COVID-19)大流行以来,越来越多的证据表明严重急性呼吸道冠状病毒综合征冠状病毒 2(SARS-CoV-2)感染与各种肺外疾病之间存在关联。然而,SARS-CoV-2 感染后引发暴发性 1 型糖尿病(FT1D)的病例报告却非常有限。我们遇到了一名 44 岁的日本女性,她在感染 SARS-CoV-2 约一周后出现 FT1D,并伴有自身免疫性甲状腺疾病(AITD)引起的亚临床甲状腺毒症。患者在转运前 4 天出现发热和流感样症状,SARS-CoV-2 抗原自我检测呈阳性。随后,她突然出现口渴、多尿和乏力,持续了 1 天,被紧急送到我们的急诊室。实验室检查结果显示她患有糖尿病酮症酸中毒(DKA),但血清糖化血红蛋白(HbA1c)水平没有明显升高(葡萄糖,930 毫克/分升;HbA1c,7.4%)。她的胰岛素分泌能力几乎完全丧失,胰岛特异性自身抗体呈阴性。内分泌检查发现了亚临床甲状腺毒症,甲状腺刺激素受体抗体呈阳性。根据上述结果,患者被诊断为 FT1D 并伴有 AITD,并立即开始接受胰岛素强化治疗,采用基础-注射皮下胰岛素方案。人类白细胞抗原分析显示了单倍型,表明患者对 FT1D 和 AITD 都有易感性。要阐明 SARS-CoV-2 感染、FT1D 和 AITD 之间的因果关系,还需要进一步的研究。然而,临床医生必须对 FT1D 和 AITD 的可能发展保持警惕,以便在 COVID-19 大流行期间准确诊断和治疗 DKA 患者。
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引用次数: 0
Efficacy and safety of switching from a dipeptidyl peptidase-4 inhibitor to oral semaglutide in Japanese patients with type 2 diabetes mellitus. 日本 2 型糖尿病患者从二肽基肽酶-4 抑制剂转为口服塞马鲁肽的疗效和安全性。
IF 1.3 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-30 eCollection Date: 2024-07-01 DOI: 10.1007/s13340-024-00734-5
Chihiro Yoneda, Junji Kobayashi, Nobuichi Kuribayashi

Background: Dipeptidyl peptidase-4 inhibitors (DPP-4is) are the most widely used oral hypoglycemic drugs in Japan. However, once-daily oral semaglutide has been reported to reduce glycated hemoglobin (HbA1c) and body weight (BW) without causing significant hypoglycemia. Here, we aimed to evaluate the efficacy and safety of switching from a DPP-4i to oral semaglutide in Japanese patients with type 2 diabetes (T2D).

Methods: We performed a single-center retrospective study of the changes in HbA1c and BW in 68 patients with T2D who were switched from a DPP-4i and took oral semaglutide for  ≥ 6 months, without changes in any other oral hypoglycemic agent.

Results: Mean HbA1c decreased from 7.8 to 7.0% (p < 0.001) and BW decreased from 74.2 to 71.2 kg (p < 0.001) over 6 months. The decrease in HbA1c was more pronounced in participants with high baseline HbA1c (r =  - 0.542, p < 0.001). There was also a trend (r = 0.236, p = 0.052) toward a decrease in BW in individuals with shorter disease duration. There were reductions in either HbA1c or BW in 65 participants (95.6%). In addition, the larger the decrease in HbA1c was, the greater was the decrease in BW (r = 0.480, p < 0.001). Eighteen participants (20.1%) discontinued the drug within 6 months, of whom 10 (11.6% of the total) did so because of suspected adverse effects and the discontinuation rate was the highest in older, non-obese patients.

Conclusions: Switching from a DPP-4i to oral semaglutide may be useful for Japanese patients with T2D who have inadequate glycemic or BW control. However, its utility may be limited by gastrointestinal adverse effects in certain patients.

背景:二肽基肽酶-4 抑制剂(DPP-4is)是日本最广泛使用的口服降糖药。然而,据报道,每日口服一次的塞马鲁肽可降低糖化血红蛋白(HbA1c)和体重(BW),但不会引起明显的低血糖。在此,我们旨在评估日本 2 型糖尿病(T2D)患者从 DPP-4i 转为口服塞马鲁肽的疗效和安全性:我们对68名T2D患者的HbA1c和体重变化进行了单中心回顾性研究,这些患者从DPP-4i转为口服司马鲁肽≥6个月,且未更换任何其他口服降糖药:平均 HbA1c 从 7.8% 降至 7.0%(p p r = - 0.542,p r = 0.236,p = 0.052),病程较短的患者体重有所下降。65 名参与者(95.6%)的 HbA1c 或体重均有所下降。此外,HbA1c 下降幅度越大,体重下降幅度也越大(r = 0.480,p 结论):对于血糖或体重控制不佳的日本 T2D 患者来说,从 DPP-4i 转为口服塞马鲁肽可能会有所帮助。然而,某些患者的胃肠道不良反应可能会限制其效用。
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引用次数: 0
Severe periodontal disease in Japanese patients with high HbA1c levels: a cross-sectional study. HbA1c 水平较高的日本患者的严重牙周病:一项横断面研究。
IF 1.3 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-28 eCollection Date: 2024-07-01 DOI: 10.1007/s13340-024-00732-7
Noboru Kurinami, Kenji Ashida, Seigo Sugiyama, Yoko Morito, Akira Yoshida, Kunio Hieshima, Fumio Miyamoto, Keizo Kajiwara, Katsunori Jinnouchi, Hideaki Jinnouchi, Masatoshi Nomura

Objective: This study aimed to investigate the relationship between plasma glucose profiles and periodontal disease (PD) severity in men and women.

Methods: We conducted a cross-sectional cohort study, enrolling all eligible patients with type 2 diabetes mellitus (T2DM) who regularly visited the outpatient department.

Results: Patients were divided into severe and non-severe PD groups. The severe PD group showed a male predominance and significantly higher hemoglobin A1c (HbA1c) levels than the non-severe PD group. The optimal HbA1c cutoff value on the receiver operating characteristic curve for predicting severe PD was 7.3% [56 mmol/mol] (sensitivity, 52%; specificity, 73%; P = 0.01). Multivariate logistic regression revealed that male sex (odds ratio [OR], 2.75; 95% confidence interval [CI], 1.19-6.34; P = 0.01) and higher HbA1c levels (OR, 3.09; 95% CI, 1.42-6.70; P < 0 .01) were independently and significantly associated with the presence of severe PD. The prevalence rates of severe PD in patients with HbA1c levels < 7.3% [56 mmol/mol] and HbA1c levels ≥ 7.3% [56 mmol/mol] were 17.4% and 53.3% in women, and 50.0% and 66.7% in men, respectively.

Conclusions: Men with T2DM had a high risk of severe PD independent of HbA1c levels. Plasma glucose management may be crucial for maintaining periodontal health in T2DM patients, particularly in women.

研究目的本研究旨在探讨男性和女性血浆葡萄糖谱与牙周病(PD)严重程度之间的关系:我们进行了一项横断面队列研究,纳入了所有定期到门诊部就诊的符合条件的 2 型糖尿病(T2DM)患者:结果:患者被分为严重和非严重并发症组。结果:患者分为严重和非严重并发症组,严重并发症组以男性为主,血红蛋白 A1c(HbA1c)水平明显高于非严重并发症组。在接收者操作特征曲线上,预测重度帕金森病的最佳 HbA1c 临界值为 7.3% [56 mmol/mol](灵敏度为 52%;特异度为 73%;P = 0.01)。多变量逻辑回归显示,男性(几率比 [OR],2.75;95% 置信区间 [CI],1.19-6.34;P = 0.01)和较高的 HbA1c 水平(OR,3.09;95% 置信区间 [CI],1.42-6.70;P < 0.01)与重度 PD 存在独立且显著的相关性。HbA1c水平<7.3%[56 mmol/mol]和HbA1c水平≥7.3%[56 mmol/mol]的患者中,重度PD的患病率在女性中分别为17.4%和53.3%,在男性中分别为50.0%和66.7%:结论:患有 T2DM 的男性罹患严重腹膜透析的风险很高,与 HbA1c 水平无关。血浆葡萄糖管理可能是维持 T2DM 患者(尤其是女性)牙周健康的关键。
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引用次数: 0
Innovations and applications of ketone body monitoring in diabetes care. 酮体监测在糖尿病护理中的创新和应用。
IF 1.3 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-28 eCollection Date: 2024-07-01 DOI: 10.1007/s13340-024-00735-4
Naoki Sakane

Ketone bodies, comprising β-hydroxybutyric acid (BHB), acetoacetate (AcAc), and acetone, play a vital role as essential energy substrates. In individuals with diabetes, ketone bodies can be elevated under various conditions, including diabetic ketoacidosis, use of sodium-glucose transporter type 2 (SGLT2) inhibitors, and extreme carbohydrate restriction. There are three methods for measuring ketone bodies. Urine ketone analysis (AcAc) is a standard clinical test, whereas blood ketone testing (BHB+AcAc) is valuable in identifying or resolving diabetic ketoacidosis. Recently, technology for measuring breath acetone has been introduced, which provides an easy means of monitoring ketogenic diets in obese individuals. The basic breath alcohol detector also reacts with breath acetone. Therefore, it is important for professional drivers taking SGLT2 inhibitors to be cautious as workplace breath alcohol detectors may show false-positive results. Conversely, if a positive result is obtained, a detailed examination of ketosis is necessary. This review provides an overview of ketone body measurements in individuals with diabetes.

酮体由β-羟丁酸(BHB)、乙酰乙酸(AcAc)和丙酮组成,作为重要的能量底物发挥着至关重要的作用。在各种情况下,包括糖尿病酮症酸中毒、使用钠-葡萄糖转运体 2 型 (SGLT2) 抑制剂和极度限制碳水化合物摄入等,糖尿病患者体内的酮体都会升高。测量酮体有三种方法。尿酮体分析(AcAc)是一种标准的临床检测方法,而血液酮体检测(BHB+AcAc)则对识别或解决糖尿病酮症酸中毒很有价值。最近,测量呼气丙酮的技术已经问世,这为监测肥胖者的生酮饮食提供了一种简便的方法。基本的呼气酒精检测仪也会与呼气丙酮发生反应。因此,服用 SGLT2 抑制剂的职业驾驶员一定要谨慎,因为工作场所的呼气酒精检测仪可能会显示假阳性结果。相反,如果检测结果呈阳性,则有必要对酮病进行详细检查。本综述概述了糖尿病患者的酮体测量。
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引用次数: 0
Pseudo-nephropathy and hyper-excretion of urinary C-peptide: an overlooked adverse effect of an angiotensin receptor-neprilysin inhibitor (ARNI). 假性肾病和尿 C 肽分泌过多:血管紧张素受体-肾素抑制剂 (ARNI) 被忽视的不良反应。
IF 1.3 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-28 eCollection Date: 2024-07-01 DOI: 10.1007/s13340-024-00730-9
Yoshito Itoh, Shigehito Suzuki, Ryohei Mineo, Sho Sasaki, Sachiko Tamba, Takuya Sugiyama, Koji Yamamoto

Sacubitril/valsartan, which is a combined angiotensin receptor-neprilysin inhibitor (ARNI), is used for the treatment of chronic heart failure and hypertension. Substrates of neprilysin are numerous, and the systemic effects of an ARNI remain to be determined. Increased urinary C-peptide (UCPR) and urinary albumin (UAlb) excretion has been reported with the use of an ARNI, but the mechanism is still unknown. We report an 84-year-old man with type 2 diabetes and hypertension. His UAlb and UCPR excretion and (to a lesser degree) the estimated glomerular filtration rate were increased after ARNI administration. They returned to basal levels after discontinuing ARNI administration. There was little or no change in glycemic control. Therefore, increased glomerular permeability and filtration could partially explain how neprilysin inhibition led to an elevation in UCPR excretion, in addition to other mechanisms, such as impairment of the renal ability to degrade C-peptide. Physicians must be cautious when interpreting the insulin secretion capability by UCPR and nephropathy by UAlb in ARNI-treated patients with diabetes.

萨库比特利/缬沙坦是一种血管紧张素受体-肾素酶联合抑制剂(ARNI),用于治疗慢性心力衰竭和高血压。肾素酶的底物很多,ARNI 的全身效应仍有待确定。有报道称,使用 ARNI 会增加尿 C 肽(UCPR)和尿白蛋白(UAlb)的排泄,但其机制尚不清楚。我们报告了一名患有 2 型糖尿病和高血压的 84 岁老人。服用 ARNI 后,他的 UAlb 和 UCPR 排泄量以及估计肾小球滤过率均有所增加(程度较轻)。停用 ARNI 后,这些指标恢复到基础水平。血糖控制几乎没有变化。因此,肾小球通透性和滤过率的增加可以部分解释肾小球溶酶抑制如何导致 UCPR 排泄增加,此外还有其他机制,如肾脏降解 C 肽的能力受损。医生在解释 ARNI 治疗的糖尿病患者 UCPR 的胰岛素分泌能力和 UAlb 的肾病时必须谨慎。
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引用次数: 0
Naming hypoglycemia: a narrative tool for young people with type 1 diabetes and their families. 为低血糖命名:1 型糖尿病青少年及其家庭的叙事工具。
IF 1.3 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-27 eCollection Date: 2024-07-01 DOI: 10.1007/s13340-024-00731-8
Francisco Sobral do Rosário, Marta Soares, Filipe Mesquita, João Filipe Raposo

Objective: Hypoglycemia constitutes a communication barrier between youth with type 1 diabetes, their family members and health professionals. A narrative tool may contribute to a more effective communication.

Methods: Semi-structured interviews with six open-ended questions using narrative techniques collect and analyze (thematic and comparative analysis) different ways of "naming" the lived experience of hypoglycemia.

Results: 103 participants, 40 with type 1 Diabetes aged 10-18 years (17 female), 63 relatives (40 female). Group 1 (G1), 10-14 years old (n = 21), Group 2 (G2), 15-18 years old (n = 19), Group 3 (G3) relatives, 30-59 years old. G3 was divided, G3.1: female (n = 42) and G3.2: male (n = 21).G1 and G2 presents greater attention to symptoms. G1 refers a greater need for help, G2 emphasizes autonomy. G2 and G3 describes better the medical protocol. G1 and G2 refer more topics such as "discomfort", "frustration", "obligation", "difficulty in verbalizing", G3 refers to "gilt", "fear" and "responsibility". G3.1 refer more "symptoms", "responsibility", "fault", "incapacity".

Conclusions: A narrative tool enhances the singularity of a common experience, proving itself useful to adolescents, relatives, and healthcare professionals.

Practice implications: In addition to gathering information that is usually acquired empirically, a narrative tool exposes knowledge gaps and may allow implementing intervention strategies.

目的:低血糖是 1 型糖尿病患者、其家人和医疗专业人员之间的沟通障碍。叙事工具可能有助于更有效的沟通:方法:采用叙事技术,通过六个开放式问题进行半结构式访谈,收集并分析(主题分析和比较分析)"命名 "低血糖生活经历的不同方式:103 名参与者,40 名 10-18 岁的 1 型糖尿病患者(17 名女性),63 名亲属(40 名女性)。第一组(G1),10-14 岁(21 人);第二组(G2),15-18 岁(19 人);第三组(G3),30-59 岁。G3 分为 G3.1:女性(n = 42)和 G3.2:男性(n = 21)。G1 表示更需要帮助,G2 则强调自主性。G2 和 G3 更好地描述了医疗方案。G1 和 G2 提及更多的话题,如 "不适"、"沮丧"、"义务"、"难以用语言表达",G3 提及 "憔悴"、"恐惧 "和 "责任"。G3.1 提及更多的是 "症状"、"责任"、"过错 "和 "能力缺失":结论:叙事工具增强了共同经历的独特性,对青少年、亲属和医护人员都很有用:实践意义:除了收集通常通过经验获得的信息外,叙事工具还能揭示知识差距,从而实施干预策略。
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引用次数: 0
Advances in basic research on glucagon and alpha cells. 胰高血糖素和α细胞基础研究的进展。
IF 1.3 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-02-26 eCollection Date: 2024-07-01 DOI: 10.1007/s13340-024-00696-8
Yoshitaka Hayashi

The regulation of plasma amino acid levels by glucagon in humans first attracted the attention of researchers in the 1980s. Recent basic research using animal models of glucagon deficiency suggested that a major physiological role of glucagon is the regulation of amino acid metabolism rather than to increase blood glucose levels. In this regard, novel feedback regulatory mechanisms that are mediated by glucagon and amino acids have recently been described between islet alpha cells and the liver. Increasingly, hyperglucagonemia in humans with diabetes and/or nonalcoholic fatty liver diseases is reported to likely be a compensatory response to hepatic glucagon resistance. Severe glucagon resistance due to a glucagon receptor mutation in humans causes hyperaminoacidemia and islet alpha cell expansion combined with pancreatic hypertrophy. Notably, a recent report showed that the restoration of glucagon resistance by liver transplantation resolved not only hyperglucagonemia, but also pancreatic hypertrophy and other metabolic disorders. The mechanisms that regulate islet cell proliferation by amino acids largely remain unelucidated. Clarification of such mechanisms will increase our understanding of the pathophysiology of diseases related to glucagon.

20 世纪 80 年代,胰高血糖素对人体血浆氨基酸水平的调节首次引起了研究人员的注意。最近利用胰高血糖素缺乏动物模型进行的基础研究表明,胰高血糖素的主要生理作用是调节氨基酸代谢,而不是提高血糖水平。在这方面,最近描述了胰高血糖素和氨基酸在胰岛α细胞和肝脏之间的新型反馈调节机制。越来越多的报道称,糖尿病和/或非酒精性脂肪肝患者体内的高胰高血糖素血症可能是肝脏胰高血糖素抵抗的代偿反应。人类胰高血糖素受体突变导致的严重胰高血糖素抵抗会引起高氨基酸血症、胰岛α细胞扩张和胰腺肥大。值得注意的是,最近的一份报告显示,通过肝移植恢复胰高血糖素抵抗不仅能解决高胰高血糖素血症,还能解决胰腺肥大和其他代谢紊乱。氨基酸调节胰岛细胞增殖的机制在很大程度上仍未阐明。阐明这些机制将加深我们对胰高血糖素相关疾病的病理生理学的理解。
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引用次数: 0
Acknowledgement to the Reviewers. 向审稿人致谢。
IF 2.2 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-01-12 eCollection Date: 2024-01-01 DOI: 10.1007/s13340-023-00690-6
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引用次数: 0
期刊
Diabetology International
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