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: 3.12). 02/2010; 27(2):136-42. DOI: 10.1111/j.1464-5491.2009.02894.x
Source: PubMed


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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    • "In patients with T2DM, both renal and hepatic glucose release are increased as a result of increased gluconeogenesis. The relative increase in renal gluconeogenesis is thought to be substantially greater than in hepatic gluconeogenesis (300% vs 30%) [2]. Renal glycogenolysis is minimal in healthy individuals but may play a role in increased renal glucose release in patients with T2DM, due to accumulation of glycogen in diabetic kidneys [5] "
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    ABSTRACT: The kidneys play an important role in regulating glucose homeostasis through utilization of glucose, gluconeogenesis, and glucose reabsorption via sodium glucose co-transporters (SGLTs) and glucose transporters. The renal threshold for glucose excretion (RTG) is increased in patients with type 2 diabetes mellitus (T2DM), possibly due to upregulation of SGLT2 and SGLT1 expression. The resulting increase in renal glucose reabsorption is thought to contribute to the maintenance of hyperglycemia in patients with T2DM. Selective SGLT2 inhibitors reduce the RTG, thereby increasing glucosuria, and have demonstrated favorable efficacy and safety in patients with T2DM inadequately controlled with diet and exercise and other glucose-lowering treatments.
    Full-text · Article · Oct 2014 · Metabolism
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    • "The kidneys contribute to glucose homeostasis through several mechanisms, including gluconeogenesis, glucose use, and glucose reabsorption from the glomerular filtrate [10]. During glucose reabsorption, for example, approximately 180 L of plasma is filtered daily through the kidneys, which is equivalent to approximately 180 g of glucose, if the average plasma glucose concentration is 100 mg/dL [11]. Under normal physiological conditions, this filtered glucose is almost completely reabsorbed by renal tubular epithelial cells; thus, there is no glucose in urine [11,12]. "
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    ABSTRACT: Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder, and a major public health problem that is rapidly increasing in prevalence. Although a wide range of pharmacotherapies for glycemic control is now available, management of T2DM remains complex and challenging. The kidneys contribute immensely to glucose homeostasis by reabsorbing glucose from the glomerular filtrate. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new class of antidiabetic agents that inhibit glucose absorption from the kidney independent of insulin, offer a unique opportunity to improve the outcomes of patients with T2DM. In this review, we provide an overview of two globally-approved SGLT2 inhibitors, dapagliflozin and canagliflozin, and discuss their effects and safety. This information will help clinicians to decide whether these drugs will benefit their patients.
    Full-text · Article · Aug 2014 · Diabetes & metabolism journal
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    • "Key kidney functions that help achieve glucose homeostasis involve renal gluconeogenesis, glucose uptake from the circulation, and glucose reabsorption from the glomerular filtrate [38]. Given an average plasma glucose concentration of approximately 100 mg/dL (5.5 mmol/L) and a normal glomerular filtration rate of approximately 180 L/day, healthy individuals filter in the region of 180 g/day of glucose. "
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    ABSTRACT: Although hyperglycemia is a key therapeutic focus in the management of patients with type 2 diabetes mellitus (T2DM), many patients experience sub-optimal glycemic control. Current glucose-lowering agents involve the targeting of various body organs. Sodium glucose co-transporter type 2 (SGLT2) inhibitors target the kidney, reduce renal glucose reabsorption, and increase urinary glucose elimination, thus lowering glucose blood levels. This review examines some of the key efficacy and safety data from clinical trials of the main SGLT2 inhibitors approved or currently in development, and provides a rationale for the use of SGLT2 inhibitors in the treatment of T2DM.
    Preview · Article · Oct 2013
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