Banting Lecture 2001

McGarry, J. Denis

doi:10.2337/diabetes.51.1.7

Cited by 1,435Pancreatic function and diabetesDiabetes Treatment and ManagementDiabetes, Cardiovascular Risks, and Lipoproteins

Banting Lecture 2001

McGarry, J. Denis·2002·Diabetes

DOI 10.2337/diabetes.51.1.7

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Abstract

Readers of this journal do not need to be reminded of the explosive increase in obesity/type 2 diabetes syndromes and their attendant staggering public health costs that are currently afflicting developed countries. Because of this alarming development and what it portends for the future if left unchecked, the American Diabetes Association, together with its counterparts around the world, as well as the World Health Organization, are faced with the daunting challenge of finding answers to two huge questions. First, what is the pathophysiological basis for these disorders? Second, why is their rate of appearance accelerating so rapidly at this particular juncture of human history, and what, if anything, can we do to intervene? The primary focus of this lecture will be on the first of these issues. I want to emphasize at the outset that I do not plan to dwell exclusively on our own studies in this area. Instead, I shall try to incorporate recent developments from a variety of other laboratories working in the field. Although these will of necessity have to be highly selective, I hope that collectively they will illustrate how we have come to a relatively new and exciting way of thinking about the etiology of type 2 diabetes. It has been said in literary circles that James Joyce’s Ulysses is probably the most frequently opened and least read book that has ever been published. In a similar vein, I sometimes think that the question of what causes type 2 diabetes might be one of the most frequently asked and least satisfactorily answered in the history of diabetes research. This is not meant to be an arrogant statement, nor indeed does it imply that I have a magical solution to the question at hand. Rather, it simply reflects the fact that at the dawn of …

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One common feature of diverse insulin-resistant states is an elevation in nonesterified fatty acids.
“One common feature of diverse insulin-resistant states is an elevation in nonesterified fatty acids (11).”
From A High-Fat Diet Coordinately Downregulates Genes Required for Mitochondrial Oxidative Phosphorylation in Skeletal Muscle (2005) · cites this paper as [11]
Elevated circulating lipid and inflammatory cytokines usually occur prior to development of hyperinsulinemia and hyperglycemia during progression of type 2 diabetes.
“Although many studies demonstrated the effect of hyperglycemia on increased generation of ROS and mitochondrial fission in a variety of cell types (26, 48), elevated circulating lipid and inflammatory cytokines usually occur prior to the development of hyperinsulinemia and hyperglycemia during the progression of type 2 diabetes (27, 38).”
From Mitochondrial Fission Contributes to Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle (2012) · cites this paper as [27]
Increased intramyocellular fat content and fatty acid metabolites have a pivotal role in the development of skeletal muscle insulin resistance.
“an increased intramyocellar fat content and fatty acid metabolites have been shown to play a pivotal role in the development of insulin resistance in skeletal muscle [11–15].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [12]
Dysregulation of fatty acid metabolism has a central role in the development of insulin resistance in skeletal muscle.
“Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle.”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [12]
Chronically elevated plasma free fatty acid levels cause insulin resistance in skeletal muscle.
“It is well established that chronically elevated plasma FFA levels cause insulin resistance in skeletal muscle [1, 12, 14, 62–65].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [12]

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β-Cell Deficit and Increased β-Cell Apoptosis in Humans With Type 2 Diabetes
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β-Cell Function in Subjects Spanning the Range from Normal Glucose Tolerance to Overt Diabetes: A New Analysis
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Hepatic expression of malonyl-CoA decarboxylase reverses muscle, liver and whole-animal insulin resistance
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Remission of human type 2 diabetes requires decrease in liver and pancreas fat content but is dependent upon capacity for β cell recovery
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Authors: McGarry, J. D.
Affiliations: The University of Texas Southwestern Medical Center (US)
Corresponding author: McGarry, J. Denis
ORCID: McGarry, J. Denis
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2002-01-01
Volume: 51
Issue: 1
Pages: 7-18
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diabetes.51.1.7
OpenAlex: W2430143578
Cited by: 1,435
References: 96
Citations by year: 2026: 10 · 2025: 15 · 2024: 27 · 2023: 30 · 2022: 39 · 2021: 30 · 2020: 38 · 2019: 24 · 2018: 26 · 2017: 35 · 2016: 52 · 2015: 61 · 2014: 60 · 2013: 84 · 2012: 86
FWCI: 93.35
Type: journal article
Language: en
Open access: closed
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: type 2 diabetes, obesity, pathophysiology, disease acceleration, diabetes prevention
MeSH terms: Insulin Secretion, Blood Glucose, Diabetes Mellitus, Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Glucose, Homeostasis, Humans, Insulin, Islets of Langerhans, Models, Biological, Obesity, Triglycerides

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