Abstract
Renal proximal tubules reabsorb glucose from the glomerular filtrate and release it back into the circulation. Modulation of glomerular filtration and renal glucose disposal are some of the insulin actions, but little is known about a possible insulin effect on tubular glucose reabsorption. This review is aimed at synthesizing the current knowledge about insulin action on glucose handling by proximal tubules. Method. A systematic article selection from Medline (PubMed) and Embase between 2008 and 2019. 180 selected articles were clustered into topics (renal insulin handling, proximal tubule glucose transport, renal gluconeogenesis, and renal insulin resistance). Summary of Results. Insulin upregulates its renal uptake and degradation, and there is probably a renal site-specific insulin action and resistance; studies in diabetic animal models suggest that insulin increases renal SGLT2 protein content; in vivo human studies on glucose transport are few, and results of glucose transporter protein and mRNA contents are conflicting in human kidney biopsies; maximum renal glucose reabsorptive capacity is higher in diabetic patients than in healthy subjects; glucose stimulates SGLT1, SGLT2, and GLUT2 in renal cell cultures while insulin raises SGLT2 protein availability and activity and seems to directly inhibit the SGLT1 activity despite it activating this transporter indirectly. Besides, insulin regulates SGLT2 inhibitor bioavailability, inhibits renal gluconeogenesis, and interferes with Na+K+ATPase activity impacting on glucose transport. Conclusion. Available data points to an important insulin participation in renal glucose handling, including tubular glucose transport, but human studies with reproducible and comparable method are still needed.
Highlights
Diabetes global prevalence almost doubled in the last three decades
Distal segment SGLT (PTs) reabsorb glucose following its glomerular filtration, through the sodium-glucose linked transporters (SGLTs), mainly the SGLT2 located on the luminal surface of PT cells [5]
Written in English, assessing primary or secondary insulin action on glucose handling by PTs in humans, animal models, tissues, or cell cultures were eligible for inclusion
Summary
Diabetes global prevalence almost doubled in the last three decades. This disorder is a major cause of kidney failure, up to 44% of world end-stage renal disease, beyond ten times dialysis need and renal transplantation [1]. Kidneys are the leading organs involved in insulin clearance from the systemic circulation [2]. They contribute to endogenous glucose production through gluconeogenesis, primarily in proximal tubule (PT) cells [3] under glucose and insulin regulation [4]. Renal glucose handling depends on glucose glomerular filtration [6, 7] and on the degree of kidney damage [8]
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