Removal of necessary solutes prompts the next step in the filtration process: reabsorption. The tubular portion of the nephron consists of the proximal tubule, the loop of Henle and the distal tubule.
Distal tubules and proximal tubules perform opposing functions. While the proximal tubule reabsorbs solutes into the blood supply, the distal tubule secretes waste solutes that will be excreted in urine.
Glucose reabsorption takes place in the proximal tubule of the nephron, a tube leading out of Bowman's capsule. The cells that line the proximal tubule recapture valuable molecules, including glucose. The mechanism of reabsorption is different for different molecules and solutes. For glucose there are two processes involved: the process whereby glucose is reabsorbed across the apical membrane of the cell, meaning the membrane of the cell that faces out onto the proximal tubule, and then the mechanism whereby the glucose is shunted across the opposite membrane of the cell into the bloodstream.
Embedded in the apical membrane of the cells lining the proximal tubule are proteins that act like tiny molecular pumps to drive sodium ions out of the cell and potassium ions in, expending stored cellular energy in the process. This pumping action ensures that the concentration of sodium ions is much higher in the proximal tubule than in the cell, like pumping water to a storage tank atop a hill so it can do work as it flows back down.
Solutes dissolved in water naturally tend to diffuse from areas of high to low concentration, which causes the sodium ions to flow back into the cell. It has the enzymes to store glucose as glycogen and the glycolytic enzymes necessary to use those stores. The renal cortex has the glucosephosphatase, an enzyme that is necessary to release glucose into the bloodstream. The renal cortex works with the liver to regulate glucose hemostasis.
The cortex does not have the correct enzymes to store and use glycogen. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab, 14 1 Gerich J. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications.
Diabet Med, 27 2 Triplitt C. Our medical articles are the result of the hard work of our editorial board and our professional authors. Strict editorial standards and an effective quality management system help us to ensure the validity and high relevance of all content. Read more about the editorial team, authors, and our work processes. Already registered? Your email address will not be published. Lecturio is using cookies to improve your user experience.
By continuing use of our service you agree upon our Data Privacy Statement. Are you more of a visual learner? Your path to achieve medical excellence. Study for medical school and boards with Lecturio. Votes: 6, average: 4. These basic functions are critical to regulation of fluid and electrolyte balance, body fluid osmolality, acid-based balance, excretion of metabolic waste and foreign chemicals, arterial pressure, hormone secretion, and, most relevant to this discussion, glucose balance.
The basic urine-forming unit of the kidney is the nephron, which serves to filter water and small solutes from plasma and reabsorb electrolytes, amino acids, glucose, and protein. The nephron, of which there are approximately 1 million in each kidney, consists of a filtering apparatus the glomerulus that is connected to a long tubular portion that reabsorbs and conditions the glomerular ultrafiltrate.
Fluid filtered from the glomerular capillaries flows into the tubular portion, which is made up of a proximal tubule, the Loop of Henle, and the distal tubule, all of which assist in reabsorbing essential substances and converting filtered fluid into urine. Evaluation of renal function is an important part of care, and with that, creatinine clearance CrCl or glomerular filtration rate GFR , most frequently estimated eGFR , are considered most useful in determining the degree of renal insufficiency and the stage of chronic kidney disease in accordance with the National Kidney Foundation classification system.
Since alterations in all renal functions ie, filtration, secretion, reabsorption, endocrine and metabolic function have been associated primarily with GFR, this quantitative index may be used to measure any functional changes that result from kidney-related disease progression, therapeutic intervention, or toxic insult. As described in greater detail in the first article in this supplement, maintenance of glucose homeostasis is crucial in preventing pathological consequences that may result from hyperglycemia or hypoglycemia.
Chronically uncontrolled hyperglycemia leads to a higher risk of macrovascular and microvascular complications, such as cardiovascular disease, nephropathy, neuropathy, and retinopathy. As alluded to previously, the kidneys are capable of synthesizing and secreting many important hormones eg, renin, prostaglandins, kinins, erythropoietin and are involved in a wide variety of metabolic processes such as activation of vitamin D3, gluconeogenesis, and metabolism of numerous endogenous compounds eg, insulin, steroids.
Renal release of glucose into the circulation is the result of glycogenolysis and gluconeogenesis. Glycogenolysis involves the breakdown of glycogen to glucosephosphate from precursors eg, lactate, glycerol, amino acids and its subsequent hydrolysis via glucosephosphatase to free glucose. Conversely, gluconeogenesis involves formation of glucosephosphate from those same precursors and subsequent conversion to free glucose.
As such, the breakdown of hepatic glycogen leads to release of glucose, whereas the breakdown of muscle glycogen leads to release of lactate. Lactate generated via glycolysis of glucose by blood cells, the renal medulla, and other tissues may be absorbed by organs and reformed into glucose.
With regard to glucose utilization, the kidney may be perceived as 2 separate organs, with glucose utilization occurring predominantly in the renal medulla and glucose release limited to the renal cortex. These activities are separated as a result of differences in the distribution of various enzymes along the nephron.
To this point, cells in the renal medulla which, like the brain, are obligate users of glucose have significant glucose-phosphorylating and glycolytic enzyme activity, and can therefore phosphorylate and accumulate glycogen. However, since these cells lack glucosephosphatase and other gluconeogenic enzymes, they cannot release free glucose into the circulation.
On the other hand, renal cortex cells do possess gluconeogenic enzymes including glucosephosphatase , and therefore can make and release glucose into the circulation. But because these cells have little phosphorylating capacity, they cannot synthesize glycogen. The magnitude of renal glucose release in humans is somewhat unclear, with inconclusive evidence regarding the contribution of the kidneys to total body gluconeogenesis.
In addition to their important role in gluconeogenesis, the kidneys contribute to glucose homeostasis by filtering and reabsorbing glucose. Under normal conditions, the kidneys retrieve as much glucose as possible, rendering the urine virtually glucose free. Glucosuria may also occur at lower plasma glucose concentrations in certain conditions of hyperfiltration eg, pregnancy , but as a consequence of hyperfiltration rather than significant hyperglycemia.
The transport of glucose a polar compound with positive and negative charged areas, making it soluble in water into and across cells is dependent on specialized carrier proteins in 2 gene families: the facilitated glucose transporters GLUTs and the sodium-coupled glucose cotransporters SGLTs.
These transporters control glucose transport and reabsorption in several tissue types, including the proximal renal tubule, small intestine, blood-brain barrier, and peripheral tissues Table.
SGLTs, on the other hand, mediate active transport of glucose against a concentration gradient by means of cotransport with sodium. This predominant role of SGLT2 in renal reabsorption of glucose raises the prospect of therapeutically blocking this protein in patients with diabetes. In examining disorders involving renal glucose transport, gene mutations within SGLTs lead to inherited disorders of renal glucosuria, including familial primary renal glucosuria FRG and glucose-galactose malabsorption GGM.
FRG, an autosomal recessive or autosomal dominant disorder resulting from several different SGLT2 mutations, is characterized by persistent glucosuria in the absence of hyperglycemia or general renal tubular dysfunction. Even the most severe form of FRG type O , where nonfunctioning mutations within the SGLT2 gene result in a complete absence of renal tubular glucose reabsorption, is associated with a favorable prognosis.
Because FRG is generally asymptomatic, affected individuals are identified through routine urinalysis. GGM, a more serious autosomal recessive disease caused by mutation of the SGLT1 transporter, is characterized by intestinal symptoms that manifest within the first few days of life and result from failure to absorb glucose and galactose from the intestinal tract.
The resultant severe diarrhea and dehydration may be fatal if a glucose- and galactose-free diet is not initiated. In some patients with GGM, glucosuria is present but typically mild, while in others, no evidence of abnormal urinary glucose excretion exists, affirming the minor role of SGLT1 in renal glucose reabsorption of glucose. Gene mutations involving GLUTs are associated with more severe consequences, as these transporters are more widespread throughout the major organ systems.
Compared with SGLT2 and SGLT1, which are present mostly in the renal system, GLUT2 is a widely distributed facilitative glucose transporter that has a key role in glucose homeostasis through its involvement in intestinal glucose uptake, renal reabsorption of glucose, glucosensing in the pancreas, and hepatic uptake and release of glucose. Because GLUT2 is involved in the tubular reabsorption of glucose, glucosuria is a feature of the nephropathy. While renal glucose reabsorption is a glucose-conserving mechanism in normal physiologic states, it is known to contribute to hyperglycemia in conditions such as T2DM.
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