Regulation of hepatic glucose production and the role of gluconeogenesis in humans: is the rate of gluconeogenesis constant?

  title={Regulation of hepatic glucose production and the role of gluconeogenesis in humans: is the rate of gluconeogenesis constant?},
  author={Frank Q. Nuttall and Angela L Ngo and Mary C. Gannon},
  journal={Diabetes/Metabolism Research and Reviews},
We have been interested in the metabolic effects of ingested fuels, both in normal subjects and in people with type 2 diabetes. Recently, we have become interested in the regulation of glucose production and the regulation of gluconeogenesis in particular. We are not aware of a recent comprehensive review of these topics. Therefore, we have reviewed the currently available literature. 

Regulation of Glucose Production in the Pathogenesis of Type 2 Diabetes

Recent experiments in canine models indicate that the direct effects of insulin on the liver are dominant over the indirect effects to regulate glucose production, and insulin-independent mechanisms by which hepatocytes sense intrahepatic carbohydrate levels to regulate carbohydrate disposal are identified.

The regulation of glucose metabolism: implications and considerations for the assessment of glucose homeostasis in rodents.

A discussion on the regulation of rodent glucose metabolism, highlighting key differences and similarities that exist between rodents and humans and some of the issues and considerations associated with assessing glucose homeostasis and insulin action are outlined.

The Hormones of Glucose Metabolism

This paper will examine the hormones that directly regulate or impact glucose metabolism and an overview of glycemic disorders is provided.

Role of proteins in insulin secretion and glycemic control.

Effects of 11β-hydroxysteroid dehydrogenase-1 inhibition on hepatic glycogenolysis and gluconeogenesis.

The data suggest that inhibition of 11β-HSD1 may be of therapeutic value in the treatment of diseases characterized by insulin resistance and excessive hepatic glucose production.

Nutritional regulation of the anabolic fate of amino acids within the liver in mammals: concepts arising from in vivo studies

The present review examines the utilisation of amino acids (AA) within the liver in various physiopathological states in mammals and how the fates of AA are regulated.

Influence of plasma macronutrient levels on hepatic metabolism: role of regulatory networks in homeostasis and disease states

A detailed dynamic model for hepatic metabolism incorporating the regulatory mechanisms at signaling and transcriptional level is developed and indicates that higher levels of macronutrient in plasma results in impairment of metabolic functions due to perturbations in the regulatory circuit.



Gluconeogenesis in type 2 diabetes.

There is now considerable evidence that increased hepatic glucose output rather than reduced peripheral glucose uptake is the primary factor responsible for both fasting and postprandial

Renal gluconeogenesis: its importance in human glucose homeostasis.

Early work in animals and humans is summarized, methodological problems in assessing renal glucose release in vivo are discussed, and results of recent human studies are presented that provide evidence that the kidney may play a significant role in carbohydrate metabolism under both physiological and pathological conditions.

Novel concepts in insulin regulation of hepatic gluconeogenesis.

Signaling mechanisms and nuclear events that transduce the regulation of gluconeogenic enzymes and coactivator protein PGC-1 are focused on.

Regulation of glucose production by the liver.

This review focuses on the short- and long-term regulation glucose-6-phosphatase and its substrate cycle counter-part, glucokinase, and includes the regulation of GLUT 2, which facilitates the final step in the transport of glucose out of the liver and into the bloodstream.

Glucagon and regulation of glucose metabolism.

  • G. JiangBei B. Zhang
  • Medicine, Biology
    American journal of physiology. Endocrinology and metabolism
  • 2003
As a counterregulatory hormone for insulin, glucagon plays a critical role in maintaining glucose homeostasis in vivo in both animals and humans and has been pursued extensively in recent years as potential targets for the therapeutic treatment of diabetes.

Pathways of carbon flux in gluconeogenesis.

Although the classical pathways of gluconeogenesis are now well understood, they alone do not account for the rate of incorporation of isotopes from labeled precursors into glucose or for the

Carbohydrate metabolism in non-insulin-dependent diabetes mellitus.

The physiology of normal carbohydrate metabolism and the pathophysiology of abnormalities in diabetes mellitus is reviewed.

Estimating gluconeogenic rates in NIDDM.

  • B. Landau
  • Biology
    Advances in experimental medicine and biology
  • 1993
To measure the rate of gluconeogenesis in humans directly, one must administer and determine the specific activity or the enrichment in an intermediate in the gluconeogenic process and in the glucose

Type 2 diabetic patients have increased gluconeogenic efficiency to substrate availability, but intact autoregulation of endogenous glucose production

  • I. ToftT. Jenssen
  • Medicine, Biology
    Scandinavian journal of clinical and laboratory investigation
  • 2005
Althought type 2 diabetics have increased EGP and increased lactate gluconeogenesis, the hepatic autoregulation of EGP during increased substrate‐induced gluc oneogenesis seems to be intact.