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J Endocrinol. 2019 Jun 1;241(3):189-199. doi: 10.1530/JOE-18-0566.

Glucose mediates insulin sensitivity via a hepatoportal mechanism in high-fat-fed rats.

Author information

1
The University of Sydney, Charles Perkins Centre, School of Life and Environmental Sciences, Sydney, New South Wales, Australia.
2
The University of Sydney, Charles Perkins Centre, School of Medical Sciences, Sydney, New South Wales, Australia.

Abstract

Poor nutrition plays a fundamental role in the development of insulin resistance, an underlying characteristic of type 2 diabetes. We have previously shown that high-fat diet-induced insulin resistance in rats can be ameliorated by a single glucose meal, but the mechanisms for this observation remain unresolved. To determine if this phenomenon is mediated by gut or hepatoportal factors, male Wistar rats were fed a high-fat diet for 3 weeks before receiving one of five interventions: high-fat meal, glucose gavage, high-glucose meal, systemic glucose infusion or portal glucose infusion. Insulin sensitivity was assessed the following day in conscious animals by a hyperinsulinaemic-euglycaemic clamp. An oral glucose load consistently improved insulin sensitivity in high-fat-fed rats, establishing the reproducibility of this model. A systemic infusion of a glucose load did not affect insulin sensitivity, indicating that the physiological response to oral glucose was not due solely to increased glucose turnover or withdrawal of dietary lipid. A portal infusion of glucose produced the largest improvement in insulin sensitivity, implicating a role for the hepatoportal region rather than the gastrointestinal tract in mediating the effect of glucose to improve lipid-induced insulin resistance. These results further deepen our understanding of the mechanism of glucose-mediated regulation of insulin sensitivity and provide new insight into the role of nutrition in whole body metabolism.

KEYWORDS:

high-fat-fed rats; insulin resistance; metabolic adaptation; nutrition; portal vein

PMID:
30939450
DOI:
10.1530/JOE-18-0566

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