Uninephrectomy and sodium‐glucose cotransporter 2 inhibitor administration delay the onset of hyperglycemia DOI Creative Commons
Yuri Ishizaki, M Kikuchi, Koichi Kaikita

и другие.

Physiological Reports, Год журнала: 2024, Номер 12(21)

Опубликована: Ноя. 1, 2024

The kidneys are essential for glucose homeostasis, as they perform gluconeogenesis, utilize glucose, and reabsorb glucose. Reabsorption is performed by SGLT2, which responsible about 90%. However, little known how renal handling altered in patients with chronic kidney disease (CKD). SGLT2 inhibitors have demonstrated efficacy suppressing CKD progression clinical trials, but their mechanisms not fully understood. Therefore, this study aimed to evaluate each uninephrectomy (UNx) inhibitor affects blood concentrations SGLTs dynamics rats type 2 diabetes mellitus. Male were divided into four treatment groups: sham + placebo, dapagliflozin, UNx dapagliflozin. There few group differences food intake or body weight, continued rise the whereas was delayed several weeks largely suppressed mRNA expression significantly lower group, SGLT1 did differ. Dapagliflozin alter expression. In animal models of diabetes, reabsorption appears likely be a major contributor development hyperglycemia.

Язык: Английский

Transforming obesity: The advancement of multi-receptor drugs DOI

Christine M. Kusminski,

Diego Pérez–Tilve, Timo D. Müller

и другие.

Cell, Год журнала: 2024, Номер 187(15), С. 3829 - 3853

Опубликована: Июль 1, 2024

Язык: Английский

Процитировано

30

Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection DOI Open Access
Alessio Mazzieri, Francesca Porcellati,

Francesca Timio

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 3969 - 3969

Опубликована: Апрель 3, 2024

Diabetic kidney disease (DKD) is a chronic microvascular complication in patients with diabetes mellitus (DM) and the leading cause of end-stage (ESKD). Although glomerulosclerosis, tubular injury interstitial fibrosis are typical damages DKD, interplay different processes (metabolic factors, oxidative stress, inflammatory pathway, fibrotic signaling, hemodynamic mechanisms) appears to drive onset progression DKD. A growing understanding pathogenetic mechanisms, development new therapeutics, opening way for era nephroprotection based on precision-medicine approaches. This review summarizes therapeutic options linked specific molecular mechanisms including renin-angiotensin-aldosterone system blockers, SGLT2 inhibitors, mineralocorticoid receptor antagonists, glucagon-like peptide-1 agonists, endothelin aldosterone synthase inhibitors. In nephroprotection, these drugs, as pillars personalized medicine, can improve renal outcomes enhance quality life individuals

Язык: Английский

Процитировано

14

A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease DOI Creative Commons
Viknesh Selvarajah,

Darren Robertson,

Lars Hansen

и другие.

Kidney International, Год журнала: 2024, Номер 106(6), С. 1170 - 1180

Опубликована: Авг. 31, 2024

Abstract

Cotadutide is a glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist that may improve kidney function in patients with type 2 diabetes (T2D) chronic disease (CKD). In this phase 2b study, T2D CKD ,estimated glomerular filtration rate [eGFR] of 20 or more under 90 mL/min per 1.73 m2 urinary albumin-to-creatinine ratio [UACR] over 50 mg/g) were randomized 1:1:1:1:1 to 26 weeks treatment standard care plus subcutaneous cotadutide up-titrated to100, 300, 600 μg, placebo daily (double-blind), the GLP-1 semaglutide 1 mg once-weekly (open-label).The co-primary endpoints absolute percentage change versus UACR from baseline end week 14. Among 248 patients, mean age 67.1 years, 19% female, eGFR was 55.3 m2, geometric 205.5 mg/g (coefficient variation 270.0), 46.8% receiving concomitant sodium–glucose co-transporter inhibitors. dose-dependently reduced 14, reaching significance at 300 μg (−43.9% [95%confidence interval −54.7 −30.6]) (−49.9% [−59.3 −38.4]) placebo; effects sustained 26. Serious adverse events balanced across arms. Safety tolerability comparable semaglutide. Thus, our study shows T2Dand CKD, significantly on top an acceptable profile, suggesting protective benefits need confirmation larger study.

Язык: Английский

Процитировано

8

The renal glucagon receptor is essential to kidney metabolic and homeostatic functions DOI
Ellen F. Carney

Nature Reviews Nephrology, Год журнала: 2024, Номер 20(4), С. 203 - 203

Опубликована: Фев. 29, 2024

Язык: Английский

Процитировано

4

Inhibiting Tgf-Β1/ Smad Pathways by Targeting Acsl4 /Gpx4 Axis Dependent Ferroptosis Attenuates Diabetic Renal Fibrosis DOI
Zhihua Wu, Ting Yu, Lin Yan

и другие.

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0

Female glucagon receptor knockout mice are prone to steatosis but resistant to weight gain when fed a MASH‐promoting GAN diet and a high‐fat diet DOI Creative Commons
Katrine D. Galsgaard, Emilie Elmelund, Jenna Elizabeth Hunt

и другие.

Physiological Reports, Год журнала: 2025, Номер 13(4)

Опубликована: Фев. 1, 2025

Abstract Glucagon is secreted from the pancreatic alpha cells and regulates not only hepatic glucose production, but also lipid amino acid metabolism. Thus, glucagon provides a switch storage towards breakdown fueling production during fasting. However, effects of genetic deletion receptor on metabolism are unclear. We therefore assessed parameters in fasted non‐fasted male female mice with permanent whole‐body ( Gcgr −/− mice). To investigate whether tolerated diet promoting metabolic dysfunction‐associated steatohepatitis (MASH) steatosis, we fed Gubra Amylin Nonalcoholic (GAN) high‐fat (HFD), respectively. found that standard chow showed hypercholesterolemia increased liver fat (borderline significant mice, remaining groups). In state these changes were insignificant due to fasting‐induced steatosis. When challenged GAN HFD, prone steatosis dyslipidemia resistant weight gain. Taken together, our data highlight as an important physiological regulator just glucose,

Язык: Английский

Процитировано

0

The effect of retatrutide on kidney parameters in participants with type 2 diabetes and/or obesity DOI Creative Commons
Hiddo J.L. Heerspink,

Zeqing Lu,

Yu Du

и другие.

Kidney International Reports, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0

Renal tubular epithelial IGFBP7 interacts with PKM2 to drive renal lipid accumulation and fibrosis DOI
Ju-tao Yu, Shuai-shuai Xie, Xiaoyu Shen

и другие.

Molecular Therapy, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0

Survodutide for the Treatment of Obesity DOI Creative Commons
Mikhail Kosiborod, Elke Platz, Sean Wharton

и другие.

JACC Heart Failure, Год журнала: 2024, Номер unknown

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

2

Disruption of branched-chain amino acid homeostasis promotes the progression of DKD via enhancing inflammation and fibrosis-associated epithelial-mesenchymal transition DOI

Xiaoqing Deng,

Chao Tang, Ting Fang

и другие.

Metabolism, Год журнала: 2024, Номер unknown, С. 156037 - 156037

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

1