Role of the kidney in normal glucose homeostasis and in
the hyperglycaemia of diabetes mellitus: therapeutic
J. E. Gerich
University of Rochester School of Medicine, Rochester, NY, USA
Accepted 10 November 2009
Considerable data have accumulated over the past 20 years, indicating that the human kidney is involved in the regulation of
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’,
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
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
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)
Keywords gluconeogenesis, kidney, sodium glucose co-transporter 2, Type 2 diabetes mellitus
Abbreviations FFA, free fatty acid; FRG, familial renal glucosuria; GLUT, glucose transporter; SGLT1, sodium–glucose
co-transporter 1; SGLT2, sodium glucose co-transporter 2; SGLTs, sodium–glucose co-transporters; T2DM, Type 2
diabetes mellitus; Tm, transport maximum
The kidney’s involvement in glucose homeostasis was first
described in the 1930s . Despite the large body of evidence
amassed over the ensuing years, the kidney is still often
overlooked as an important player in glucose metabolism.
However, awarenessof renal
homeostasis is likely to increase in the near future because
from the glomerular filtrate [the sodium–glucose co-transporter
2 (SGLT2) inhibitors]. This article reviews our current
understanding of the role of the kidney in normal glucose
homeostasis and abnormalities in patients with Type 2 diabetes
mellitus (T2DM). Medline was searched from 1989 to present
using theterms ‘renal gluconeogenesis’,
utilization’, ‘diabetes mellitus’ and ‘glucose transporters’.
Overview of renal glucose homeostasis
The human kidney is involved in the regulation of glucose
homeostasis and in abnormalities found in diabetes mellitus via
three different mechanisms: (i) release of glucose into the
circulation via gluconeogenesis; (ii) uptake of glucose from the
Correspondence to: John E. Gerich, MD, University of Rochester School of
Medicine, 601 Elmwood Ave, Box MED ⁄ CRC, Rochester, NY 14642, USA.
Re-use of this article is permitted in accordance with the terms and
conditions set out at http://www3.interscience.wiley.com/author_resources/
ª 2010 The Author.
Journal compilation ª 2010 Diabetes UK. Diabetic Medicine, 27, 136–142
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DIABETICMedicine Role of the kidney in glucose homeostasis • J. E. Gerich
ª 2010 The Author.
Journal compilation ª 2010 Diabetes UK. Diabetic Medicine, 27, 136–142