Bolinder J, Ljunggren Ö, Kullberg J, Johansson L, Wilding J, Langkilde AM, et al. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab. 2012;97:1020–31.

CAS  PubMed  Google Scholar 

Ferrannini E. Sodium-glucose co-transporters and their inhibition: clinical physiology. Cell Metab. 2017;26:27–38.

CAS  PubMed  Google Scholar 

Zhao S, Lo CS, Miyata KN, Ghosh A, Zhao XP, Chenier I, et al. Overexpression of Nrf2 in renal proximal tubular cells stimulates sodium-glucose cotransporter 2 expression and exacerbates dysglycemia and kidney injury in diabetic mice. Diabetes. 2021;70:1388–403.

CAS  PubMed  Google Scholar 

Wang XX, Levi J, Luo Y, Myakala K, Herman-Edelstein M, Qiu L, et al. SGLT2 protein expression is increased in human diabetic nephropathy: SGLT2 protein expression is increased in human diabetic nephropathy: SGLT2 protein inhibition decreases renal lipid accumulation, inflammation, and the development of nephropathy in diabetic mice. J Bio Chem. 2017;292:5335–48.

CAS  Google Scholar 

Umino H, Hasegawa K, Minakuchi H, Muraoka H, Kawaguchi T, Kanda T, et al. High basolateral glucose increases sodium-glucose cotransporter 2 and reduces sirtuin-1 in renal tubules through glucose transporter-2 detection. Sci Rep. 2018;8:6791.

PubMed  PubMed Central  Google Scholar 

Chichger H, Cleasby ME, Srai SK, Unwin RJ, Debnam ES, Marks J. Experimental type II diabetes and related models of impaired glucose metabolism differentially regulate glucose transporters at the proximal tubule brush border membrane. Exp Physiol. 2016;101:731–42.

CAS  PubMed  Google Scholar 

Polidori D, Sha S, Mudaliar S, Ciaraldi TP, Ghosh A, Vaccaro N, et al. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study. Diabetes Care. 2013;36:2154–61.

CAS  PubMed  PubMed Central  Google Scholar 

Bakris GL, Fonseca VA, Sharma K, Wright EM. Renal sodium-glucose transport: role in diabetes mellitus and potential clinical implications. Kidney Int. 2009;75:1272–7.

CAS  PubMed  Google Scholar 

Ahwin P, Martinez D. The relationship between SGLT2 and systemic blood pressure regulation. Hypertens Res. 2024;47:2094–103.

PubMed  PubMed Central  Google Scholar 

Mazidi M, Rezaie P, Gao HK, Kengne AP. Effect of sodium-glucose cotransport-2 inhibitors on blood pressure in people with type 2 diabetes mellitus: a systematic review and meta-analysis of 43 randomized control trials with 22 528 patients. J Am Heart Assoc. 2017;6:e004007.

PubMed  PubMed Central  Google Scholar 

Wu JH, Foote C, Blomster J, Toyama T, Perkovic V, Sundström J, et al. Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2016;4:411–9.

CAS  PubMed  Google Scholar 

Pereira MJ, Eriksson JW. Emerging role of SGLT-2 inhibitors for the treatment of obesity. Drugs. 2019;79:219–30.

CAS  PubMed  PubMed Central  Google Scholar 

Majewski C, Bakris GL. Blood pressure reduction: an added benefit of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes. Diabetes Care. 2015;38:429–30.

PubMed  PubMed Central  Google Scholar 

Drucker DJ. Prevention of cardiorenal complications in people with type 2 diabetes and obesity. Cell Metab. 2024;36:338–53.

CAS  PubMed  Google Scholar 

Vallon V, Platt KA, Cunard R, Schroth J, Whaley J, Thomson SC, et al. SGLT2 mediates glucose reabsorption in the early proximal tubule. J Am Soc Nephrol. 2011;22:104–12.

CAS  PubMed  PubMed Central  Google Scholar 

Carbone S, O’Keefe JH, Lavie CJ. SGLT2 inhibition, visceral adiposity, weight, and type 2 diabetes mellitus. Obesity. 2020;28:1173.

PubMed  Google Scholar 

Obata A, Kubota N, Kubota T, Iwamoto M, Sato H, Sakurai Y, et al. Tofogliflozin improves insulin resistance in skeletal muscle and accelerates lipolysis in adipose tissue in male mice. Endocr J. 2016;157:1029–42.

CAS  Google Scholar 

Garretson JT, Szymanski LA, Schwartz GJ, Xue B, Ryu V, Bartness TJ. Lipolysis sensation by white fat afferent nerves triggers brown fat thermogenesis. Mol Metab. 2016;5:626–34.

CAS  PubMed  PubMed Central  Google Scholar 

Bartness TJ, Liu Y, Shrestha YB, Ryu V. Neural innervation of white adipose tissue and the control of lipolysis. Front Neuroendocrinol. 2014;35:473–93.

CAS  PubMed  PubMed Central  Google Scholar 

Willows JW, Blaszkiewicz M, Townsend KL. The sympathetic innervation of adipose tissues: regulation, functions, and plasticity. Compr Physiol. 2023;13:4985–5021.

PubMed  PubMed Central  Google Scholar 

Migliorini RH, Garofalo MA, Kettelhut IC. Increased sympathetic activity in rat white adipose tissue during prolonged fasting. Am J Physiol. 1997;272:R656–61.

CAS  PubMed  Google Scholar 

Izumida Y, Yahagi N, Takeuchi Y, Nishi M, Shikama A, Takarada A, et al. Glycogen shortage during fasting triggers liver-brain-adipose neurocircuitry to facilitate fat utilization. Nat Commun. 2013;4:2316.

PubMed  Google Scholar 

Uno K, Katagiri H, Yamada T, Ishigaki Y, Ogihara T, Imai J, et al. Neuronal pathway from the liver modulates energy expenditure and systemic insulin sensitivity. Science. 2006;312:1656–9.

CAS  PubMed  Google Scholar 

Dong M, Chen H, Wen S, Yuan Y, Yang L, Li Y, et al. The neuronal and non-neuronal pathways of sodium-glucose cotransporter-2 inhibitor on body weight-loss and insulin resistance. Diabetes Metab Syndr Obes Targets Ther. 2023;16:425–35.

CAS  Google Scholar 

Young JB, Landsberg L. Suppression of sympathetic nervous system during fasting. Science. 1977;196:1473–5.

CAS  PubMed  Google Scholar 

Young JB. Developmental plasticity in sympathetic nervous system response to fasting in adipose tissues of male rats. Metab Clin Exp. 2003;52:1621–6.

CAS  PubMed  Google Scholar 

Matthews JR, Herat LY, Magno AL, Gorman S, Schlaich MP, Matthews VB. SGLT2 inhibitor-induced sympathoexcitation in white adipose tissue: a novel mechanism for beiging. Biomedicines. 2020;8:514.

CAS  PubMed  PubMed Central  Google Scholar 

Yang X, Liu Q, Li Y, Ding Y, Zhao Y, Tang Q, et al. Inhibition of the sodium-glucose co-transporter SGLT2 by canagliflozin ameliorates diet-induced obesity by increasing intra-adipose sympathetic innervation. Br J Pharm. 2021;178:1756–71.

CAS  Google Scholar 

Shi Z, Wang YF, Wang GH, Wu YL, Ma CL. Paraventricular nucleus is involved in the central pathway of adipose afferent reflex in rats. Can J Physiol Pharm. 2016;94:534–41.

CAS  Google Scholar 

Tomita I, Kume S, Sugahara S, Osawa N, Yamahara K, Yasuda-Yamahara M, et al. SGLT2 inhibition mediates protection from diabetic kidney disease by promoting ketone body-induced mTORC1 inhibition. Cell Metab. 2020;32:404–19.e6.

CAS  PubMed  Google Scholar 

Packer M. Role of ketogenic starvation sensors in mediating the renal protective effects of SGLT2 inhibitors in type 2 diabetes. J Diabetes Complications. 2020;34:107647.

PubMed  Google Scholar 

Koepke JP, DiBona GF. High sodium intake enhances renal nerve and antinatriuretic responses to stress in spontaneously hypertensive rats. Hypertension. 1985;7:357–63.

CAS  PubMed  Google Scholar 

Agmon Y, Dinour D, Brezis M. Disparate effects of adenosine A1- and A2-receptor agonists on intrarenal blood flow. Am J Physiol. 1993;265:F802–6.

CAS  PubMed  Google Scholar 

Iwamoto T, Kita S, Zhang J, Blaustein MP, Arai Y, Yoshida S, et al. Salt-sensitive hypertension is triggered by Ca2+ entry via Na+/Ca2+ exchanger type-1 in vascular smooth muscle. Nat Med. 2004;10:1193–9.

CAS  PubMed  Google Scholar 

Tsurumi Y, Tamura K, Tanaka Y, Koide Y, Sakai M, Yabana M, et al. Interacting molecule of AT1 receptor, ATRAP, is colocalized with AT1 receptor in the mouse renal tubules. Kidney Int. 2006;69:488–94.

CAS  PubMed  Google Scholar 

Wakui H, Tamura K, Matsuda M, Bai Y, Dejima T, Shigenaga A, et al. Intrarenal suppression of angiotensin II type 1 receptor binding molecule in angiotensin II-infused mice. Am J Physiol Ren Physiol. 2010;299:F991–1003.

CAS  Google Scholar 

Nagahisa T, Yamaguchi S, Kosugi S, Homma K, Miyashita K, Irie J, et al. Intestinal epithelial NAD+ biosynthesis regulates GLP-1 production and postprandial glucose metabolism in mice. Endocrinology. 2022;163:bqac023.

PubMed  Google Scholar 

Katholi RE, McCann WP, Woods WT. Intrarenal adenosine produces hypertension via renal nerves in the one-kidney, one clip rat. Hypertension. 1985;7:I88–93.

CAS  PubMed