Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. May 15, 2021; 12(5): 556-568
Published online May 15, 2021. doi: 10.4239/wjd.v12.i5.556
Renal gluconeogenesis in insulin resistance: A culprit for hyperglycemia in diabetes
Rajni Sharma, Swasti Tiwari
Rajni Sharma, Swasti Tiwari, Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
Author contributions: Sharma R and Tiwari S contributed to the conception of the review; Sharma R performed the literature search and drafted the manuscript; Tiwari S and Sharma R performed the editing and proofreading of the manuscript; both authors approved the final version of the manuscript for submission.
Supported by The Indian Council of Medical Research, No. 55/4/4/CARE-KD/2018/NCD-II; and the Council of Scientific & Industrial Research, No. 09/590/(0159)/2016-EMR-1.
Conflict-of-interest statement: Authors declare no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Swasti Tiwari, PhD, Professor, Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, 4th Floor, PMMSY Building, Lucknow 226014, India. tiwaris@sgpgi.ac.in
Received: February 16, 2021
Peer-review started: February 16, 2021
First decision: March 16, 2021
Revised: March 27, 2021
Accepted: April 23, 2021
Article in press: April 23, 2021
Published online: May 15, 2021
Abstract

Renal gluconeogenesis is one of the major pathways for endogenous glucose production. Impairment in this process may contribute to hyperglycemia in cases with insulin resistance and diabetes. We reviewed pertinent studies to elucidate the role of renal gluconeogenesis regulation in insulin resistance and diabetes. A consensus on the suppressive effect of insulin on kidney gluconeogenesis has started to build up. Insulin-resistant models exhibit reduced insulin receptor (IR) expression and/or post-receptor signaling in their kidney tissue. Reduced IR expression or post-receptor signaling can cause impairment in insulin’s action on kidneys, which may increase renal gluconeogenesis in the state of insulin resistance. It is now established that the kidney contributes up to 20% of all glucose production via gluconeogenesis in the post-absorptive phase. However, the rate of renal glucose release excessively increases in diabetes. The rise in renal glucose release in diabetes may contribute to fasting hyperglycemia and increased postprandial glucose levels. Enhanced glucose release by the kidneys and renal expression of the gluconeogenic-enzyme in diabetic rodents and humans further point towards the significance of renal gluconeogenesis. Overall, the available literature suggests that impairment in renal gluconeogenesis in an insulin-resistant state may contribute to hyperglycemia in type 2 diabetes.

Keywords: Renal gluconeogenesis, Insulin-resistance, Insulin, Insulin receptor signaling, Diabetes, Gluconeogenic enzymes

Core Tip: Recently, investigators have begun elucidating the role of renal gluconeogenesis in physiology and pathology. Recent evidence suggests a significant role of the kidney in glucose metabolism under pathological conditions, such as insulin resistance and diabetes. This review summarizes the findings from the literature that have enhanced our knowledge related to the significance of renal gluconeogenesis in normal and pathological states.