Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: Therapeutic implications

University of Rochester School of Medicine, Rochester, NY 14642, USA.
Diabetic Medicine (Impact Factor: 3.06). 02/2010; 27(2):136-42. DOI: 10.1111/j.1464-5491.2009.02894.x
Source: PubMed

ABSTRACT Considerable data have accumulated over the past 20 years, indicating that the human kidney is involved in the regulation of glucose via gluconeogenesis, taking up glucose from the circulation, and by reabsorbing glucose from the glomerular filtrate. In light of the development of glucose-lowering drugs involving inhibition of renal glucose reabsorption, this review summarizes these data. Medline was searched from 1989 to present using the terms ‘renal gluconeogenesis’, ‘renal glucose utilization’, ‘diabetes mellitus’ and ‘glucose transporters’. The human liver and kidneys release approximately equal amounts of glucose via gluconeogenesis in the post-absorptive state. In the postprandial state, although overall endogenous glucose release decreases substantially, renal gluconeogenesis increases by approximately twofold. Glucose utilization by the kidneys after an overnight fast accounts for ∼10% of glucose utilized by the body. Following a meal, glucose utilization by the kidney increases. Normally each day, ∼180 g of glucose is filtered by the kidneys; almost all of this is reabsorbed by means of sodium–glucose co-transporter 2 (SGLT2), expressed in the proximal tubules. However, the capacity of SGLT2 to reabsorb glucose from the renal tubules is finite and, when plasma glucose concentrations exceed a threshold, glucose appears in the urine. Handling of glucose by the kidney is altered in Type 2 diabetes mellitus (T2DM): renal gluconeogenesis and renal glucose uptake are increased in both the post-absorptive and postprandial states, and renal glucose reabsorption is increased. Specific SGLT2 inhibitors are being developed as a novel means of controlling hyperglycaemia in T2DM.
Diabet. Med. 27, 136–142 (2010)

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    • "Reabsorption of glucose from the glomerular filtrate increases in proportion to the plasma glucose concentration until the maximum transport capacity of the tubules (the transport maximum for glucose [Tm G ]) is reached, above which excess glucose is lost in the urine (Basile, 2011; Mather & Pollock, 2011). In people with T2DM, Tm G is increased by up to 20%, so urinary glucose excretion (UGE) begins to occur at higher than normal plasma glucose levels (Gerich, 2010). Studies of renal cells isolated from urine have shown that SGLT2 and GLUT2 expression is increased in patients with T2DM (Rahmoune et al., 2005). "
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