Role of human liver, kidney, and skeletal muscle in postprandial glucose homeostasis

Abstract

. Role of human liver, kidney, and skeletal muscle in postprandial glucose homeostasis. Am J Physiol Endocrinol Metab 282: E419-E427, 2002; 10.1152/ ajpendo.00032.2001.-Recent studies indicate a role for the kidney in postabsorptive glucose homeostasis. The present studies were undertaken to evaluate the role of the kidney in postprandial glucose homeostasis and to compare its contribution to that of liver and skeletal muscle. Accordingly, we used the double isotope technique along with forearm and renal balance measurements to assess systemic, renal, and hepatic glucose release as well as glucose uptake by kidney, skeletal muscle, and splanchnic tissues in 10 normal volunteers after ingestion of 75 g of glucose. We found that, during the 4.5-h postprandial period, 22 Ϯ 2 g (30 Ϯ 3% of the ingested glucose) were initially extracted by splanchnic tissues. Of the remaining 53 Ϯ 2 g that entered the systemic circulation, 19 Ϯ 3 g were calculated to have been taken up by skeletal muscle and 7.5 Ϯ 1.7 g by the kidney (26 Ϯ 3 and 10 Ϯ 2%, respectively, of the ingested glucose). Endogenous glucose release during the postprandial period (16 Ϯ 2 g), calculated as the difference between overall systemic glucose appearance and the appearance of ingested glucose in the systemic circulation, was suppressed 61 Ϯ 3%. Surprisingly, renal glucose release increased twofold (10.6 Ϯ 2.5 g) and accounted for ϳ60% of postprandial endogenous glucose release. Hepatic glucose release (6.7 Ϯ 2.2 g), the difference between endogenous and renal glucose release, was suppressed 82 Ϯ 6%. These results demonstrate a hitherto unappreciated contribution of the kidney to postprandial glucose homeostasis and indicate that postprandial suppression of hepatic glucose release is nearly twofold greater than had been calculated in previous studies (42 Ϯ 4%), which had assumed that there was no renal glucose release. We postulate that increases in postprandial renal glucose release may play a role in facilitating efficient liver glycogen repletion by permitting substantial suppression of hepatic glucose release.gluconeogenesis; glycogenolysis; glucose disposal CONSIDERABLE INFORMATION has recently accumulated regarding postprandial glucose homeostasis. It appears that about one-third of ingested carbohydrate is immediately taken up by splanchnic tissues (5, 22, 33-35, 37, 38, 44, 60). Of the remaining two-thirds of the ingested carbohydrate that enters the systemic circulation, some is extracted by the liver (23), but most is taken up by peripheral tissues. Limb balance measurements indicate that skeletal muscle is the predominant site for this peripheral glucose disposal, being responsible for about one-fourth of the ingested carbohydrate (5, 26, 33-35, 37, 38, 44). The fate of the remaining 40% of the ingested carbohydrate is less clear.In addition to tissue uptake of ingested carbohydrate, another important factor for postprandial glucose homeostasis is suppression of the release of glucose endogenously produced by gluconeogenesis and breakdown of ...

Abnormal expressions of circadian-clock and circadian clock-controlled genes in the livers and kidneys of long-term, high-fat-diet-treated mice

“…The kidneys mainly play an important role in maintaining body fluid and water homeostasis, as well as glucose production. [50][51][52][53] Obesity may potentiate the development and progression of secondary focal segmental glomerulosclerosis. 54,55 Recently, circadian-clock genes were shown to act on E-box elements present in the promoter region of the NHE3 and to play a direct role in regulating NHE3 gene expression in the kidneys.…”

Renal Gluconeogenesis

“…After meal ingestion, endogenous glucose production decreases, and the ingested carbohydrate load is taken up by various tissues, mainly the liver and muscles (42,66). The role of the kidney in postprandial glucose metabolism has recently been investigated (67). Seemingly, renal glucose release paradoxically increases postprandially and it accounts for Ͼ50% of the endogenous glucose release for several hours.…”

“…The mechanism responsible for this increase in renal glucose release remains to be determined, but it could involve postprandial increases in sympathetic nervous system activity (68) and increases in the availability of gluconeogenic precursors (e.g., lactate and amino acids). Renal glucose uptake apparently does not play a major role in postprandial glucose uptake, because it accounted for Ͻ10% of the disposition of the ingested glucose load (67).…”

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“…All those 25 donors had evidence of different types and stages of diabetic retinopathy. The male percentage of them was 56.3%, the mean interval between kidney donation, and development of high albuminuria, very high albuminuria, and/or decreased creatinine clearance was 10.1 ± 4.6 years (range, 4-21 y) and the mean interval between the development of DM and high albuminuria, very high albuminuria, and or decreased eGFR below 70 mL/min was 6 ± 3.9 y (range, [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. The percentage of high albuminuria, very high albuminuria, and/or decreased creatinine clearance below 70 mL/min is significantly higher in our study than a UKPDS64 study, which showed 30.8% in a study of 5100 T2DM patients with 2 kidneys enrolled in it.…”

“…Yet traditionally, the kidneys have not been considered an important source of glucose (except during acidosis or after prolonged fasting), with most clinical discussions on glucose dysregulation centering on the intestine, pancreas, liver, adipose tissue, and muscle. 2 However, the significance of the kidneys' contribution to glucose homeostasis, under both physiologic and pathologic conditions, has become well-recognized, and is thought to involve functions beyond glucose uptake and release. Besides the liver, the kidney is the only organ capable of generating sufficient glucose (gluconeogenesis) to release into the circulation, and it is also responsible for filtration and subsequent reabsorption or excretion of glucose.…”