Renal glucose production and utilization: new aspects in humans

Abstract

Summary According to current textbook wisdom the liver is the exclusive site of glucose production in humans in the postabsorptive state. Although many animal and in vitro data have documented that the kidney is capable of gluconeogenesis, production of glucose by the human kidney in the postabsorptive state has generally been regarded as negligible. This traditional view is based on net balance measurements which, other than after a prolonged fast or during metabolic acidosis, showed no significant net renal glucose release. However, recent studies have refuted this view by combining isotopic and balance techniques, which have demonstrated that renal glucose production accounts for 25 % of systemic glucose production. Moreover, these studies indicate that glucose production by the human kidney is stimulated by epinephrine, inhibited by insulin and is excessive in diabetes mellitus. Since renal glucose release is largely, if not exclusively, due to gluconeogenesis, it is likely that the kidney is as important a gluconeogenic organ as the liver. The most important renal gluconeogenic precursors appear to be lactate, glutamine and glycerol. The implications of these recent findings on the understanding of the physiology and pathophysiology of human glucose metabolism are discussed. [Diabetologia (1997) 40: 749-757].

Renal amino acid, fat and glucose metabolism in type 1 diabetic and non-diabetic humans: effects of acute insulin withdrawal

“…We failed to observe any effect of acute insulin deficiency on renal glucose production in type 1 diabetic subjects, but as noted above it is possible that more severe hypoinsulinaemia could have promoted renal glucose production. In particular, it should be noticed that under the current conditions insulin withdrawal did not augment circulating epinephrine concentrations and that epinephrine has been reported to stimulate renal glucose production; and blood levels of epinephrine increase in severe diabetic derangement, such as ketoacidosis [4,6]. Table 5 Arterial plasma concentrations and whole-body appearance rates for palmitate and femoral and renal net palmitate balances, and palmitate release and uptake rates in five diabetic subjects with and without insulin and in six control subjects Enhanced lipolysis and uncontrolled ketogenesis following insulin deprivation can lead to diabetic ketoacidosis.…”

“…The renal contribution to endogenous glucose production has been a matter of much controversy [4][5][6][7][8][9][10][11][12]28]. Much of the confusion in all likelihood has arisen from the fact that measurements across the renal bed, because of the high renal blood flow of around 1 l/min, are highly susceptible to methodological imprecision as regards analysis of differences in arteriovenous glucose concentrations and dilution of tracers.…”

“…Until recently it was assumed that the primary tissues participating in these events were liver (increased glucose production and ketogenesis), adipose tissue (increased lipolysis) and muscle (increased proteolysis) [1][2][3]. Several reports have suggested that in addition the kidney may be an important component in the regulation of intermediary metabolism, in particular glucose metabolism [4]. This renewed interest in the metabolic role of the kidney was fuelled by a study by Cersosimo et al [5] who used arteriovenous balance and isotopic dilution techniques to report that in postabsorptive dogs renal glucose utilisation and production each accounted for close to 30% of total glucose turnover in the presence of net balances close to zero.…”

Peripheral insulin resistance develops in transgenic rats overexpressing phosphoenolpyruvate carboxykinase in the kidney

“…Interestingly moderate increase of insulin suppressed liver, but not kidney, PEPCK mRNA in both the PEPCK transgenic and control rats. As has been previously suggested [32], this implies that kidney PEPCK is not as insulin responsive as liver PEPCK and that increased renal glucose production can be a substantial contributor to glucose turnover [36,37]. It has been shown that in patients undergoing liver transplantation endogenous glucose production falls about 50% after removal of the liver, representing renal glucose production [38].…”

Emerging Roles of Cadmium and Heme Oxygenase in Type-2 Diabetes and Cancer Susceptibility

“…Accumulation of cadmium in both liver and kidney is a cause for concern as these two organs contribute to the maintenance of blood glucose levels (Gerich 2010;DeFronzo et al 2012). In the post absorptive state, kidney and liver supply an equal amount of glucose into blood circulation (Stumvoll et al 1997;Gerich 2010;DeFronzo et al 2012). Further, cadmium accumulation in kidney and RPE could contribute to early onset of diabetic nephropathy and retinopathy as seen in the Torres Strait (Australia) population who had elevated dietary cadmium exposures (Satarug et al 2000b;HaswellElkins et al 2007a,b;Haswell-Elkins et al 2008).…”