The DOI matches its Crossref record; 96 of the 96 references it cites were found in a registry or an index.
Banting Lecture 2001
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 …
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“Considerable data implicate a causative role for elevated plasma FFA level in insulin resistance in skeletal muscle.”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [12]
In the citing paper
“The important role of elevated plasma FFA in the pathogenesis of insulin resistance is now well established [12, 14, 57].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [12]
Citations
Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419
Leptin and the regulation of body weight in mammals
Friedman, J. M., & Halaas, J. L. (1998) · Nature · doi:10.1038/27376 · Cited by 5,405
Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress"?
Neel, J. V. (1962) · Europe PMC (PubMed Central) · Cited by 3,172
Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714
Obesity and the regulation of energy balance
Spiegelman, B. M., & Flier, J. S. (2001) · Cell · doi:10.1016/s0092-8674(01)00240-9 · Cited by 2,398
Pathogenesis of NIDDM. A balanced overview.
DeFronzo, R. A., Bonadonna, R. C., & Ferrannini, E. (1992) · Diabetes Care · doi:10.2337/diacare.15.3.318 · Cited by 2,085
The Mitochondrial Carnitine Palmitoyltransferase System — From Concept to Molecular Analysis
McGarry, J. D., & Brown, N. F. (1997) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1997.00001.x · Cited by 1,616 · cited 1×
“Note that if ACC2 is physically juxtaposed to CPT I, the exercise-induced changes in malonyl-CoA concentration might be of much greater magnitude in the vicinity of CPT I than those measured in total tissue homogenates (51).”
BackgroundSelf-citationMechanism of free fatty acid-induced insulin resistance in humans.
Roden, M., Price, T. B., Perseghin, G., Petersen, K. F., Rothman, D. L., Cline, G. W., & Shulman, G. I. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118742 · Cited by 1,539
THE AMP-ACTIVATED/SNF1 PROTEIN KINASE SUBFAMILY: Metabolic Sensors of the Eukaryotic Cell?
Hardie, D. G., Carling, D., & Carlson, M. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.821 · Cited by 1,440
Dresner, A., Laurent, D., Marcucci, M., Griffin, M. E., Dufour, S., Cline, G. W., Slezak, L. A., Andersen, D. K., Hundal, R. S., Rothman, D. L., et al. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5001 · Cited by 1,311
Cited by
Sorted by citations
Items 101–125 of 125
Pendergrass, M., Bertoldo, A., Bonadonna, R., Nucci, G., Mandarino, L., Cobelli, C., & DeFronzo, R. A. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00617.2005 · Cited by 87
Fan, L., Cacicedo, J. M., & Ido, Y. (2020) · Journal of Diabetes Investigation · doi:10.1111/jdi.13303 · Cited by 86
CPT I overexpression protects L6E9 muscle cells from fatty acid-induced insulin resistance
Sebastián, D., Herrero, L., Serra, D., Asins, G., & Hegardt, F. G. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00360.2006 · Cited by 89
Mohan, V., Amutha, A., Ranjani, H., Unnikrishnan, R., Datta, M., Anjana, R. M., Staimez, L., Ali, M. K., & Narayan, K. M. V. (2013) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2012.0259 · Cited by 82
Hypothalamic AMP-Activated Protein Kinase Regulates Glucose Production
Yang, C. S., Lam, C. K. L., Chari, M., Cheung, G. W. C., Kokorovic, A., Gao, S., Leclerc, I., Rutter, G. A., & Lam, T. K. T. (2010) · Diabetes · doi:10.2337/db10-0221 · Cited by 86
Insulin Resistance in Peripheral Tissues and the Brain: A Tale of Two Sites
Rhea, E. M., Banks, W. A., & Raber, J. (2022) · Biomedicines · doi:10.3390/biomedicines10071582 · Cited by 76
Tripathy, D., Eriksson, K. F., Orho-Melander, M., Fredriksson, J., Ahlqvist, G., & Groop, L. (2004) · Diabetologia · doi:10.1007/s00125-004-1393-8 · Cited by 74
Taylor, R., Barnes, A. C., Hollingsworth, K. G., Irvine, K. M., Solovyova, A. S., Clark, L., Kelly, T., Martin-Ruiz, C., Romeres, D., Koulman, A., et al. (2023) · Clinical Science · doi:10.1042/cs20230586 · Cited by 71
Moreno, M., Silvestri, E., De Matteis, R., de Lange, P., Lombardi, A., Glinni, D., Senese, R., Cioffi, F., Salzano, A. M., Scaloni, A., et al. (2011) · The FASEB Journal · doi:10.1096/fj.11-181982 · Cited by 71
Minireview: Mitochondrial Energetics and Insulin Resistance
Civitarese, A. E., & Ravussin, E. (2008) · Endocrinology · doi:10.1210/en.2007-1444 · Cited by 70
Krssak, M., & Roden, M. (2004) · Reviews in Endocrine and Metabolic Disorders · doi:10.1023/b:remd.0000021434.98627.dc · Cited by 68
Regulation of insulin sensitivity by adipose tissue-derived hormones and inflammatory cytokines
Ruan, H., & Lodish, H. F. (2004) · Current Opinion in Lipidology · doi:10.1097/00041433-200406000-00009 · Cited by 65
Metabolic Syndrome: Adenosine Monophosphate‐activated Protein Kinase and Malonyl Coenzyme A
Ruderman, N. B., & Saha, A. K. (2006) · Obesity · doi:10.1038/oby.2006.279 · Cited by 62
Exercise interval training: an improved stimulus for improving the physiology of pre-diabetes.
Earnest, C. P. (2008) · Medical Hypotheses · doi:10.1016/j.mehy.2008.06.024 · Cited by 58
Revisiting the diacylglycerol-induced insulin resistance hypothesis
Amati, F. (2012) · Obesity Reviews · doi:10.1111/j.1467-789x.2012.01036.x · Cited by 59
Mitochondrial fat oxidation is essential for lipid-induced inflammation in skeletal muscle in mice
Warfel, J. D., Bermudez, E. M., Mendoza, T. M., Ghosh, S., Zhang, J., Elks, C. M., Mynatt, R., & Vandanmagsar, B. (2016) · Scientific Reports · doi:10.1038/srep37941 · Cited by 50
Cauza, E., Strehblow, C., Metz-Schimmerl, S., Strasser, B., Hanusch-Enserer, U., Kostner, K., Dunstan, D., Fasching, P., & Haber, P. (2009) · Wiener Medizinische Wochenschrift · doi:10.1007/s10354-009-0641-4 · Cited by 36
Fat tissue metabolism and adrenal steroid secretion
Lamounier-Zepter, V., & Ehrhart-Bornstein, M. (2006) · Current Hypertension Reports · doi:10.1007/s11906-006-0038-3 · Cited by 34
Mitochondrial function: use it or lose it.
Hawley, J. A., & Lessard, S. J. (2007) · Diabetologia · doi:10.1007/s00125-007-0595-2 · Cited by 32
Iozzo, P., Turpeinen, A. K., Takala, T., Oikonen, V., Solin, O., Ferrannini, E., Nuutila, P., & Knuuti, J. (2003) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-003-1215-0 · Cited by 30
Wan, Q., Wang, F., Wang, F., Guan, Q., Liu, Y., Wang, C., Feng, L., Gao, G., Gao, L., & Zhao, J. (2010) · Diabetic Medicine · doi:10.1111/j.1464-5491.2010.03107.x · Cited by 28
Biological mechanisms of stroke prevention by physical activity in type 2 diabetes
Agosti, V., Graziano, S., Artiaco, L., & Sorrentino, G. (2009) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.2008.01080.x · Cited by 25
Ohira, M., Endo, K., Saiki, A., Miyashita, Y., Terai, K., Murano, T., Watanabe, F., Tatsuno, I., & Shirai, K. (2012) · Metabolism · doi:10.1016/j.metabol.2012.03.010 · Cited by 25
Frøsig, C., Roepstorff, C., Brandt, N., Maarbjerg, S. J., Birk, J. B., Wojtaszewski, J. F. P., Richter, E. A., & Kiens, B. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90556.2008 · Cited by 21
Miyazaki, Y., De Filippis, E., Bajaj, M., Wajcberg, E., Glass, L., Triplitt, C., Cersosimo, E., Mandarino, L. J., & Defronzo, R. A. (2005) · The British Journal of Diabetes & Vascular Disease · doi:10.1177/14746514050050010601 · Cited by 18
Metadata
- 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
- 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 › Endocrinology, Diabetes and Metabolism › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review