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

Gerich JE - Diabet. Med. (2010)

Bottom Line: In the postprandial state, although overall endogenous glucose release decreases substantially, renal gluconeogenesis increases by approximately twofold.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.

View Article: PubMed Central - PubMed

Affiliation: University of Rochester School of Medicine, Rochester, NY 14642, USA. JOHNGERICH@compuserve.com

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 approximately 10% of glucose utilized by the body. Following a meal, glucose utilization by the kidney increases. Normally each day, approximately 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.

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 Renal glucose handling. Tm, transport maximum. Adapted with permission from Silverman & Turner (1992) 32. Copyright © 1992 by the American Physiological Society. By permission of Oxford University Press Inc.
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fig01:  Renal glucose handling. Tm, transport maximum. Adapted with permission from Silverman & Turner (1992) 32. Copyright © 1992 by the American Physiological Society. By permission of Oxford University Press Inc.

Mentions: Figure 1 describes the renal handling of filtered glucose 32. Glucose is freely filtered in the glomerulus, so that, as plasma glucose levels increase, the amount of glucose in the glomerular filtrate increases linearly. Reabsorption of filtered glucose also increases linearly until the maximal reabsorptive capacity is exceeded. This is often referred to as the renal threshold and equates to a filtration rate of 260–350 mg/min per 1.73 m233, which occurs at plasma glucose concentrations of 11.0 mmol/l in healthy adults 34. Above this plasma glucose concentration, the percentage of filtered glucose that is reabsorbed decreases and the percentage of the filtered load of glucose that is excreted in the urine increases, resulting in glucosuria. The ‘rounding’ of the titration curve seen around the transition from complete reabsorption to urinary excretion of excess glucose (shown in Fig. 1 as ‘splay’) can be accounted for by heterogeneity in the glomerular filtration rate and glucose reabsorptive capacity of different individual nephrons 32.


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

Gerich JE - Diabet. Med. (2010)

 Renal glucose handling. Tm, transport maximum. Adapted with permission from Silverman & Turner (1992) 32. Copyright © 1992 by the American Physiological Society. By permission of Oxford University Press Inc.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4232006&req=5

fig01:  Renal glucose handling. Tm, transport maximum. Adapted with permission from Silverman & Turner (1992) 32. Copyright © 1992 by the American Physiological Society. By permission of Oxford University Press Inc.
Mentions: Figure 1 describes the renal handling of filtered glucose 32. Glucose is freely filtered in the glomerulus, so that, as plasma glucose levels increase, the amount of glucose in the glomerular filtrate increases linearly. Reabsorption of filtered glucose also increases linearly until the maximal reabsorptive capacity is exceeded. This is often referred to as the renal threshold and equates to a filtration rate of 260–350 mg/min per 1.73 m233, which occurs at plasma glucose concentrations of 11.0 mmol/l in healthy adults 34. Above this plasma glucose concentration, the percentage of filtered glucose that is reabsorbed decreases and the percentage of the filtered load of glucose that is excreted in the urine increases, resulting in glucosuria. The ‘rounding’ of the titration curve seen around the transition from complete reabsorption to urinary excretion of excess glucose (shown in Fig. 1 as ‘splay’) can be accounted for by heterogeneity in the glomerular filtration rate and glucose reabsorptive capacity of different individual nephrons 32.

Bottom Line: In the postprandial state, although overall endogenous glucose release decreases substantially, renal gluconeogenesis increases by approximately twofold.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.

View Article: PubMed Central - PubMed

Affiliation: University of Rochester School of Medicine, Rochester, NY 14642, USA. JOHNGERICH@compuserve.com

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 approximately 10% of glucose utilized by the body. Following a meal, glucose utilization by the kidney increases. Normally each day, approximately 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.

Show MeSH
Related in: MedlinePlus