Gluconeogenesis in the amphibian retina. Lactate is preferred to glutamate as the gluconeogenic precursor

Abstract

The capacity for gluconeogenesis in the isolated amphibian retina was found to be approx. 70-fold greater with lactate than with glutamate as the gluconeogenic precursor, 1426 versus 21 pmol of glucose incorporated into glycogen/h per mg of protein. It was also found that 11-15% of the glucosyl units in glycogen are derived from C3 metabolites of the glycolytic pathway, suggesting that lactate is recycled within the retina. In concert with these metabolic observations, a full complement of the gluconeogenic enzymes was detected in retinal homogenates. These included: glucose-6-phosphatase, fructose-1,6-bisphosphatase, acetyl-CoA-dependent pyruvate carboxylase and phosphoenolpyruvate carboxykinase. Agents that regulate the rate of gluconeogenesis in hepatic tissue were tested on the retina. At concentrations of glutamate and lactate that are presumed to be relevant physiologically, it was found that vasoactive intestinal peptide, ionophore A23187 and elevated [K+] each enhanced the rate of gluconeogenesis in Ringer containing 50 microM-glutamate, whereas in Ringer containing 8.5 mM-lactate these agents inhibited the rate of gluconeogenesis. Further, it was found that the classic gluconeogenic hormone glucagon inhibited gluconeogenesis in both glutamate- and lactate-containing Ringer. Retinal energy metabolism was found to be altered in lactate-containing Ringer, in that lactate production was suppressed completely. In addition, glycogen metabolism appeared to be dependent on increased cytosolic Ca2+ and was insensitive to increased retinal cyclic AMP.

Pyruvate protects glucose‐deprived Müller cells from nitric oxide‐induced oxidative stress by radical scavenging

“…For M€ uller cells from the bullfrog a gluconeogenic pathway with lactate and glutamate as substrates was described (Goldman, 1988 and1990). However, in rabbit M€ uller cells these compounds were unable to protect against NO.…”

Glucose, lactate, and shuttling of metabolites in vertebrate retinas

“…Enzymes associated with gluconeogenesis have been found in amphibian retinas (Goldman, ), and there is evidence that Müller cells synthesize their glycogen primarily from glucose that they make by gluconeogenesis (Goldman, ; Rodriguez and Fliesler, ). Glucose‐6‐phosphatase, required for the release of glucose from a cell, also appears to be present primarily at the Müller cell endfeet (Lessell and Kuwabara, ).…”

Does abnormal glycogen structure contribute to increased susceptibility to seizures in epilepsy?

“…For PC to be effective for anaplerosis, it needs to have a supply of pyruvate, and K + is also involved in stimulating the glycolytic enzymes pyruvate kinase (Outlaw and Lowry, 1979). A direct effect of K + in stimulating gluconeogenesis and glycogen synthesis from glutamate but not from lactate has been demonstrated in amphibian retinal Muller glial cells (Goldman, 1988), where initiation of gluconeogenesis and blockade of glycolysis has been observed in response to vasoactive intestinal peptide (VIP) (Goldman, 1990). Interestingly, increased levels of VIP type-2 receptor is a features of reactive astrocytes (Nishimoto et al, 2011).…”