Kidney Function and Uremia
Sirshendu De, Anirban Roy in Hemodialysis Membranes, 2017
The human kidney performs a multitude of functions that includes: excretion of metabolic wastes; water and electrolyte balances and body fluid osmomolality; arterial pressure regulation; acid– base balance; hormonal secretion and balance; and gluconeogenesis. Along with effective renal plasma flow (ERPF), a parameter used to quantify the kidney's performance is the glomerular filtration rate (GFR). Two types of renal failures occur in humans: acute kidney injury (AKI) and chronic kidney disease (CKD). The three main reasons for acute kidney injury (AKI) are: prerenal, postrenal and renal. The precursor to toxin buildup in the human body is kidney malfunction, and this clinical syndrome is referred to as uremia resembling systemic poisoning. The challenge in kidney failure and its related treatment lies in mimicking the continuous performance of the intelligent, natural organ with a discrete treatment using an artificial substitute. It is important to understand the types of uremic toxins causing specific side effects.
Chemical Pathways, Protein Metabolism, and Interrelationships
Herschel Sidransky in Tryptophan, 2001
This chapter discusses the pathways by which L-tryptophan is metabolized into a variety of metabolites, many of which have important physiological functions. A few metabolites are cited here briefly. Quinolinic acid is involved in the regulation of gluconeogenesis. Picolinic acid is involved in normal intestinal absorption of zinc. The body’s pool of nicotinamide adenine dinucleotide (NAD) is influenced by L-tryptophan’s metabolic conversion to niacin. Finally, L-tryptophan is the precursor of several neuroactive compounds, the most important of which is serotonin (5-HT), which participates as a neurochemical substrate for a variety of normal behavioral and neuroendocrine functions. Serotonin derived from L-tryptophan allows it to become involved in behavioral effects, reflecting altered central nervous system function under conditions that alter tryptophan nutrition and metabolism.
Selected Botanicals and Plant Products That Lower Blood Glucose (Continued)
Robert Fried, Richard M. Carlton in Type 2 Diabetes, 2018
Gluconeogenesis is a metabolic pathway that leads to the synthesis of glucose from pyruvate and other noncarbohydrate precursors. Lychee may lower blood sugar levels and therefore caution is advised when taking insulin or other drugs for diabetes: consumption by mouth should be monitored closely, especially just before elective surgery. The importance of inhibiting aldose reductase is that the enzyme catalyzes the reduction of glucose to sorbitol through the polyol pathway, a process linked to the development of diabetic cataract. The journal Food and Chemical Toxicology published a report titled “Evaluation of safety and toxicity of the oligomerized polyphenol oligonol.” The report states that oligonol is an optimized phenolic product containing catechin-type monomers and lower oligomers of proanthocyanidin that result from the conversion of polyphenol polymers into oligomers. Individuals should be advised to closely monitor blood sugar when adding this botanical to a treatment regimen, and to be certain to have foodstuffs at the ready in case hypoglycemic symptoms come on.
Contribution of Gluconeogenesis to Overall Glucose Output in Diabetic and Nondiabetic Men
Published in Annals of Medicine, 1990
Agostino Consoli, Nurjahan Nurjhan
Increased hepatic glucose output is the main cause of fasting hyperglycemia in non-insulin dependent diabetes mellitus. Due to difficulties in obtaining a quantitative estimate of gluconeogenesis in vivo, the relative contribution of gluconeogenesis and glycogenolysis to this increased hepatic glucose output was unknown. The application in vivo of a new isotopic approach based on a mathematical model of the Krebs cycle enabled us to obtain a quantitative estimate of gluconeogenesis in vivo Using this approach, gluconeogenesis was found to account for 28% and 97% of overall hepatic glucose output in healthy volunteers in the postabsorptive and in the fasted state respectively. When this technique was used to compare gluconeogenesis rates in non-insulin dependent diabetes mellitus and nondiabetic patients, gluconeogenesis was found to be increased threefold in the patients with non-insulin dependent diabetes mellitus (12.7 ± 1.6 μ vs 3.6 ± 0.6 μmol/Kg/min) and to be significantly correlated with fasting plasma glucose. Furthermore, the increase in gluconeogenesis could explain more than 80% of the increase in overall hepatic glucose output in patients with non-insulin dependent diabetes mellitus. In conclusion, in non-insulin dependent diabetes mellitus, gluconeogenesis, as measured by a new isotopic technique, is increased and this increase represents the main cause for increased overall hepatic glucose output and fasting hyperglycemia.
Effects of cadmium, zinc, copper and manganese on hepatic parenchymal cell gluconeogenesis
Published in Journal of Environmental Science and Health, Part B, 1981
Margaret Tolbert, Johnson Kamalu, Garnette Draper
The effects of divalent cations on gluconeogenesis in enzy‐matically isolated rat hepatic parenchymal cells were examined. Cadmium, zinc and copper decreased glucose production from lactate (10 mM). However, manganese at 0.05 to 1.0 mM levels stimulated gluconeogenesis by the cells and reduced the effects of the Cd+2, Zn+2 and Cu+2 on gluconeogenesis. The results indicate that under these in vitro conditions the cations altered an aspect of hepatic function—gluconeogenesis from lactate.
Type 2 diabetic patients have increased gluconeogenic efficiency to substrate availability, but intact autoregulation of endogenous glucose production
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2005
Objective. An autoregulatory mechanism involving a reciprocal relationship between gluconeogenesis and glycogenolysis regulates endogenous glucose production (EGP) in healthy individuals. In type 2 diabetes, fasting hyperglycemia may be due to increased EGP. Material and methods. To examine gluconeogenesis and autoregulation of EGP in type 2 diabetes, 9 type 2 diabetics and 8 healthy controls were studied during a 3‐h infusion of 30 µmol/kg/min Na‐lactate. The diabetics were also studied during a control infusion of Na‐bicarbonate. To standardize levels of glucoregulatory hormones, plasma insulin, growth hormone, and glucagon were clamped at identical levels during the three experiments. Glucagon levels were elevated from basal levels to ∼330 ng/l when the lactate or bicarbonate infusions were started, in order to mimic the hyperglucagonemia often seen in diabetes. Lactate gluconeogenesis and total EGP were measured by infusions of [6‐3H] glucose and [U‐14C] lactate. Results. In the bicarbonate experiments, hyperglugagonemia increased lactate gluconeogenesis in the diabetic patients from 4.3±1.8 to 6.1±2.4 µmol/kg/min (p = 0.04). EGP did not change significantly (basal EGP: 15.3±3.9, EGP at the end of the study: 14.2±3.9 µmol/kg/min, p = 0.14). During both lactate experiments, plasma lactate increased more than 4‐fold. The increase in lactate gluconeogenesis was significantly higher in diabetics than in controls (values obtained at the end of experiments minus basal values: 10.8±3.6 versus 6.4±3.6 µmol/kg/min, p = 0.03). Compared with normal subjects, the diabetic patients had higher EGP values both at basal conditions (p = 0.001) and during lactate infusion (p = 0.005). Despite augmented gluconeogenesis, EGP did not change during lactate and glucagon infusion in any of the groups (diabetics, basal EGP: 15.4±2.7 versus EGP at the end of experiments: 15.6±3.6 µmol/kg/min, p>0.30. Controls, basal EGP: 11.8±0.8 versus EGP at the end of experiments: 11.6±1.9 µmol/kg/min, p>0.30). Conclusions. Althought type 2 diabetics have increased EGP and increased lactate gluconeogenesis, the hepatic autoregulation of EGP during increased substrate‐induced gluconeogenesis seems to be intact.