Insulin resistance as the core defect in type 2 diabetes mellitus
Abstract
Insulin resistance is a major contributor to the pathogenesis of type 2 diabetes and plays a key role in associated metabolic abnormalities, such as dyslipidemia and hypertension. Obesity, especially visceral adiposity, is negatively correlated with insulin sensitivity. The release of free fatty acids from adipocytes can block insulin-signaling pathways and lead to insulin resistance. In addition, recently identified adipocyte-specific chemical messengers, the adipocytokines, such as tumor necrosis factor-alpha, adiponectin, and resistin, appear to modulate the underlying insulin resistance. When insulin resistance is combined with beta-cell defects in glucose-stimulated insulin secretion, impaired glucose tolerance, hyperglycemia, or type 2 diabetes can result. The thiazolidinediones are potent peroxisome proliferator-activated receptor-gamma agonists and directly improve insulin resistance and glycemic control in patients with type 2 diabetes. Increasing evidence supports the early use of thiazolidinediones for preventing, delaying, or treating diabetes by improving insulin sensitivity and beta-cell insulin secretion.
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Recent studies suggest that visceral adiposity may play an important role in causing hepatic insulin resistance through release of fatty acids and adipocytokines to the liver via the portal vein.
“Recent studies have also suggested that visceral adiposity may play an important role in causing hepatic insulin resistance through its release of fatty acids and adipocytokines to the liver via the portal vein (28-31).”
From Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men (2006) · cites this paper as [28]
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- Authors
- Goldstein, B. J.
- Affiliations
- Thomas Jefferson University (US)
- Corresponding author
- Goldstein, Barry J
- Venue
- The American Journal of Cardiology
- Publisher
- Elsevier BV
- Published
- 2002-09
- Volume
- 90
- Issue
- 5
- Pages
- 3-10
- ISSN
- 0002-9149 (ISSN-L)
- OpenAlex
- W2084561741
- Cited by
- 432
- References
- 64
- Citations by year
- 2026: 10 · 2025: 24 · 2024: 22 · 2023: 27 · 2022: 27 · 2021: 20 · 2020: 24 · 2019: 16 · 2018: 11 · 2017: 12 · 2016: 5 · 2015: 26 · 2014: 18 · 2013: 23 · 2012: 17
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- insulin resistance, type 2 diabetes, pathogenesis, visceral fat, obesity, free fatty acids, adipocytes, insulin signaling, adipokines, TNF-α, adiponectin, resistin, beta-cell dysfunction, glucose-stimulated insulin secretion, impaired glucose tolerance, hyperglycemia, dyslipidemia, hypertension, thiazolidinediones, PPARγ, glycemic control, diabetes prevention
- MeSH terms
- Insulin Secretion, Adipose Tissue, Diabetes Mellitus, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Insulin, Insulin Resistance, Islets of Langerhans, Obesity, Risk Factors, Thiazoles
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