Cited by 343Liver Disease Diagnosis and TreatmentMetabolism, Diabetes, and CancerDiabetes, Cardiovascular Risks, and Lipoproteins

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Resolving the Paradox of Hepatic Insulin Resistance

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Santoleri, Dominic, Titchenell, Paul M.·2019·Cellular and Molecular Gastroenterology and Hepatology

DOI 10.1016/j.jcmgh.2018.10.016PMC PMC6369222

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Abstract

Insulin resistance is associated with numerous metabolic disorders, such as obesity and type II diabetes, that currently plague our society. Although insulin normally promotes anabolic metabolism in the liver by increasing glucose consumption and lipid synthesis, insulin-resistant individuals fail to inhibit hepatic glucose production and paradoxically have increased liver lipid synthesis, leading to hyperglycemia and hypertriglyceridemia. Here, we detail the intrahepatic and extrahepatic pathways mediating insulin's control of glucose and lipid metabolism. We propose that the interplay between both of these pathways controls insulin signaling and that mis-regulation between the 2 results in the paradoxic effects seen in the insulin-resistant liver instead of the commonly proposed deficiencies in particular branches of only the direct hepatic pathway.

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Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin-regulated gene expression and liver failure
Mora, A., Lipina, C., Tronche, F., Sutherland, C. D., & Alessi, D. R. (2005) · Biochemical Journal · doi:10.1042/bj20041782 · Cited by 92 · cited 1×
“In addition, deficiency in 3phosphoinositide-dependent protein kinase 1 in mouse liver causes glucose intolerance and results in liver failure.(24)”
Background
Retracted
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216
Global and societal implications of the diabetes epidemic
Zimmet, P., Alberti, K. G. M. M., & Shaw, J. (2001) · Nature · doi:10.1038/414782a · Cited by 5,883 · cited 1×
“016 Mdiabetes mellitus (T2DM) have reached epidemic proportions and continue to be a leading cause of death worldwide.(1) The liver plays a central role in the systemic regulation of glucose and lipid metabolism and aberrant hepatic insulin action is thought to be a primary driver of insulin resistance, in which highe…”
Background
Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
Cross, D. A. E., Alessi, D. R., Cohen, P., Andjelkovich, M., & Hemmings, B. A. (1995) · Nature · doi:10.1038/378785a0 · Cited by 5,244
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15593 · Cited by 4,794 · cited 1×
“Sterol regulatory element binding protein 1c (SREBP1c) is a member of the SREBP class of transcription factors that are key players in controlling cellular expression of genes required for lipid and cholesterol metabolism.(39) Insulin regulates SREBP1c by both enhancing its gene expression and post-translational proce…”
Background
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215593 · Cited by 4,092
The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor
Brown, M. S., & Goldstein, J. L. (1997) · Cell · doi:10.1016/s0092-8674(00)80213-5 · Cited by 3,834 · cited 1×
“SREBP proteins from the endoplasmic reticulum to the Golgi where it is cleaved, releasing the active part of SREBP to the nucleus where it regulates transcription.(44) SCAP is required for activation of all isoforms of SREBP and its deletion significantly reduces cholesterol and fatty acid synthesis in the liver.”
Background
Critical nodes in signalling pathways: insights into insulin action
Taniguchi, C. M., Emanuelli, B., & Kahn, C. R. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1837 · Cited by 2,760 · cited 1×
“3-phosphate kinase (PI3K)/Akt pathway is the key signaling pathway that mediates the effects of insulin on anabolic metabolism in all organisms.(17) When insulin binds to the insulin receptor (IR), it recruits and activates PI3K through insulin-receptor substrates (IRS), generating phosphatidylinositol (3,4,5)-trispho…”
Background
Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities
Sanyal, A. J., Campbell–Sargent, C., Mirshahi, F., Rizzo, W. B., Contos, M. J., Sterling, R. K., Luketic, V. A., Shiffman, M. L., & Clore, J. N. (2001) · Gastroenterology · doi:10.1053/gast.2001.23256 · Cited by 2,078 · cited 1×
“Patients with NAFLD almost universally show hyperinsulinemia.(6) In addition, both obese and diabetic human beings show a higher prevalence of NAFLD than lean ones.”
Background
Activation of a metabolic gene regulatory network downstream of mTOR complex 1
Düvel, K., Yecies, J. L., Menon, S., Raman, P., Lipovsky, A. I., Souza, A. L., Triantafellow, E., Ma, Q., Gorski, R., Cleaver, S., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.06.022 · Cited by 2,020

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Roden, 2000, Effects of free fatty acid elevation on and gluconeogenesis in humans, Endocrinol Metab, 49, 701

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“IR exacerbates hepatic glucose production and lipogenesis, leading to reduced body weight due to increased lipolysis and muscle wasting [69].”
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Background
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Background
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“Dysregulation of these liver glucose and lipid metabolic processes are primary hallmarks o f i n s u l in r e s is t a nce a n d d y s li p i da emia t h a t o c c ur i n o b e si ty a n d t y p e 2 diabetes 3,4 .”
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Background
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“43,44 Compared with CD feeding, WD-fed mice displayed hyperglycaemia, an effect that was remarkably blunted in CHP-treated animals that maintained glycaemia levels closer to physiological ranges (Fig.”
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“This also explains increased interest in targeting the amelioration of hepatic insulin resistance using novel bioactive compounds to revert T2D-related complications [7,18,19].”
BackgroundInfluential
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“The KO mice consistently had lesser than or equal body weights compared to control mice, and it was concluded that 1 3 deletion of L-PGDS gene in mice partially or fully regulate the progression of NAFLD/NASH [19].”
Background
F6P/G6P-mediated ChREBP activation promotes the insulin resistance-driven hepatic lipid deposition in zebrafish
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Background
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Background
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Background
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Background
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Background
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Background
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Background
Mechanisms and Linkage of Insulin Signaling, Resistance, and Inflammation
Hadid, K. A., Alassaf, F. A., & Abed, M. N. (2023) · Al-Mağallaẗ al-ʻirāqiyyaẗ li-l-ṣaydalaẗ · doi:10.33899/iphr.2023.144181.1065 · Cited by 11
Exploring the impacts of ketogenic diet on reversible hepatic steatosis: initial analysis in male mice
Ravaut, G., Carneiro, A., & Mounier, C. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1290540 · Cited by 12
“MAFLD development is indeed highly correlated with 10.3389/fnut.2024 .1290540 Frontiers in Nutrition 02 frontiersin.org a high dietary fat ingestion (8–10).”
BackgroundInfluential
Hepatic lipid droplet-associated proteome changes distinguish dietary-induced fatty liver from glucose tolerance in male mice
Woerkom, A. V., Harney, D., Nagarajan, S. R., Hakeem-Sanni, M. F., Lin, J., Hooke, M., Pulpitel, T., Cooney, G. J., Larance, M., Saunders, D. N., et al. (2024) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00013.2024 · Cited by 15
Co-exposure to F-53B and nanoplastics induced hepatic glucolipid metabolism disorders by the PI3K-AKT signaling pathway
Zhang, Z., Cui, M., Wang, H., Yuan, W., Liu, Z., Gao, H., Guan, X., Chen, X., Xie, L., He, Y., et al. (2025) · Environmental Pollution · doi:10.1016/j.envpol.2025.125771 · Cited by 11
An extended minimal model of OGTT: estimation of α- and β-cell dysfunction, insulin resistance, and the incretin effect
Subramanian, V., Bagger, J. I., Harihar, V., Holst, J. J., Knop, F. K., & Villsbøll, T. (2023) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00278.2023 · Cited by 11
Sarcopoterium spinosum Inhibited the Development of Non-Alcoholic Steatosis and Steatohepatitis in Mice
Wollman, A., Daniel, T., & Rosenzweig, T. (2019) · Nutrients · doi:10.3390/nu11123044 · Cited by 10
“This phenomenon suggests a selective insulin resistance of the liver, in which some arms of the insulin signaling pathway are insensitive to the hormone, while the lipogenic arm remains sensitive [29,30].”
Background
Heterocyclic amines reduce insulin-induced AKT phosphorylation and induce gluconeogenic gene expression in human hepatocytes
Walls, K. M., Hong, K. U., & Hein, D. W. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03488-2 · Cited by 10
“The liver plays a crucial role in systemic regulation of glucose and lipid metabolism, and aberrant hepatic insulin action is considered a potential primary factor in insulin resistance (Santoleri and Titchenell 2019).”
Background
Intersection of the Orphan G Protein-Coupled Receptor, GPR19, with the Aging Process
Maudsley, S. R., Walter, D., Schrauwen, C., Loon, N. V., Harputluoğlu, İ., Lenaerts, J., & McDonald, P. H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113598 · Cited by 9
Study on the action mechanism of the Polygonum perfoliatum L. on non-alcoholic fatty liver disease, based on network pharmacology and experimental validation.
Liu, G., Yang, L., Tang, Y.-F., Lin, J.-C., Wang, F., Shen, J., Chang, B., & Kong, X.-N. (2023) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2023.117330 · Cited by 9
Buddleoside-rich Chrysanthemum indicum L. extract modulates macrophage-mediated inflammation to prevent metabolic syndrome induced by unhealthy diet
Zhou, Y., Su, J., Dong, Y., He, Z., Wang, Y., Chen, S., & Lv, G. (2024) · BMC Complementary Medicine and Therapies · doi:10.1186/s12906-024-04583-2 · Cited by 9
“In insulin resistance, abnormal hepatic insulin action is thought to be the main driver of insulin resistance, requiring higher circulating insulin levels to adequately control blood glucose levels [50].”
Background
Effect of alpha linolenic acid on membrane fluidity and respiration of liver mitochondria in normoglycemic and diabetic Wistar rats
Mejía‐Zepeda, R., & Pérez-Hernández, I. H. (2020) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-020-09859-z · Cited by 9
“…this increase of glycaemia was due to insulin resistance generated by receptor desensitization derived from a hyperinsulinemia; in fact, it is known that insulin resistance is closely related to numerous metabolic disorders including the type 2 diabetes mellitus (Santoreli and Titchenell 2019).”
Background
Coffee Bioactive N‐Methylpyridinium: Unveiling Its Antilipogenic Effects by Targeting De Novo Lipogenesis in Human Hepatocytes
Giannotti, L., Stanca, E., Stanca, B. D. C., Spedicato, F., Massaro, M., Quarta, S., Rio, D. D., Mena, P. R., Siculella, L., & Damiano, F. (2024) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202400338 · Cited by 9
Ocular surface complications in diabetes: The interrelationship between insulin and enkephalin
Purushothaman, I., Zagon, I. S., Sassani, J. W., & McLaughlin, P. J. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114712 · Cited by 9
Potential protective role of let-7d-5p in atherosclerosis progression reducing the inflammatory pathway regulated by NF-κB and vascular smooth muscle cells proliferation
Aroca-Esteban, J., Souza‐Neto, F. V., Aguilar-Latorre, C., Tribaldo-Torralbo, A., González‐López, P., Ruiz‐Simón, R., Álvarez‐Villarreal, M., Ballesteros, S., de Céniga, M. V., Landete, P., et al. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2024.167327 · Cited by 8
Automated machine learning models for nonalcoholic fatty liver disease assessed by controlled attenuation parameter from the NHANES 2017–2020
Liu, L., Lin, J., Liu, L., Gao, J., Xu, G., Yin, M., Liu, X., Wu, A., & Zhu, J. (2024) · Digital Health · doi:10.1177/20552076241272535 · Cited by 9
“58,59 Furthermore, there will be hyperinsulinemia, leading to hepatic steatosis.”
Background
Metals in the human liver: An underappreciated risk factor of hepatic insulin resistance and associated pathophysiology
Kumar, R., Chinala, A., Grandhe, D., Endicott, S. J., Garcia, M. A., Campen, M. J., & Gullapalli, R. R. (2025) · Environmental Pollution · doi:10.1016/j.envpol.2025.126844 · Cited by 7
Hyperglycaemia to heart failure: molecular pathophysiology, clinical manifestations, and novel therapeutic targets for diabetic cardiomyopathy
Balakrishnan, B., Hariharapura, R. C., Nayak, V., & Divyashree, M. S. (2025) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2025.2567336 · Cited by 8
“…sensitivity and increased hepatic glucose output. β-cells secrete increasing amounts of insulin to cope with the demand to normalise glucose levels (Santoleri & titchenell, 2019). this eventually stresses out the β-cells. this and other metabolic changes ultimately lead to β-cell dysfunction and…”
Toll Like Receptor 4: A Potential Link Between Obesity and Metabolic Diseases
Alhamar, G., Razafiarison, J., Alzaïd, F., Al‐Mulla, F., & Ahmad, R. (2026) · Obesity Reviews · doi:10.1111/obr.70107 · Cited by 8
“The liver is equally critical for systemic insulin sensitivity, due to its role in glucose production and lipid metabolism [89].”
A glucose-insulin-glucagon coupled model of the isoglycemic intravenous glucose infusion experiment
Subramanian, V., Bagger, J. I., Holst, J. J., Knop, F. K., & Vilsbøll, T. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.911616 · Cited by 10
Effect of Thunbergia laurifolia water extracts on hepatic insulin resistance in high-fat diet-induced obese mice
Naowaboot, J., Nanna, U., Chularojmontri, L., Tingpej, P., & Pannangpetch, P. (2021) · Asian Pacific Journal of Tropical Biomedicine · doi:10.4103/2221-1691.306689 · Cited by 8
L-carnitine attenuates autophagic flux, apoptosis, and necroptosis in rats with dexamethasone-induced non-alcoholic steatohepatitis
Amer, A. E., Ghoneim, H. A., Abdelaziz, R. R., Shehatou, G. S. G., & Suddek, G. M. (2024) · BMC Pharmacology and Toxicology · doi:10.1186/s40360-024-00820-z · Cited by 7
“The PI3K/Akt pathway is the major insulin pathway that controls the insulin actions in the body [5, 6].”
BRCA1 regulates glucose and lipid metabolism in diabetes mellitus with metabolic dysfunction-associated steatotic liver disease via the PI3K/Akt signaling pathway
Ma, C., Yang, X., Zhang, L., Zhang, J., Zhang, Y., & Hu, X. (2025) · PLoS ONE · doi:10.1371/journal.pone.0318696 · Cited by 7
“Insulin resistance enhances the gluconeogenesis process in the liver and also promotes the synthesis of triglycerides [1] and fat [16,10].”
Impact of placental mTOR deficiency on peripheral insulin signaling in adult mice offspring
Beetch, M., Akhaphong, B., Wong, A., Clifton, B., Jo, S., Mohan, R., Abrahante, J. E., & Alejandro, E. U. (2023) · Journal of Molecular Endocrinology · doi:10.1530/jme-23-0035 · Cited by 6
“Preclinical studies have shown that impaired hepatic Akt signaling is associated with hyperinsulinemia and insulin resistance (Santoleri & Titchenell 2019).”
Background
Phosphoenolpyruvate carboxykinase-1 targeted siRNA promotes wound healing in type 2 diabetic mice by restoring glucose homeostasis
Bajaj, G., Singh, V., Sagar, P., Gupta, R., & Singhal, N. K. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.132504 · Cited by 7
Relationship between four insulin resistance surrogates and regression to normoglycemia from prediabetes among Chinese adults: A longitudinal Cohort Study
Yang, L., Feng, Y., Wang, Y., Liu, C., & Gao, D. (2024) · Endocrine · doi:10.1007/s12020-024-03947-5 · Cited by 7
“Intrahepatic fat accumulation leads to hepatic IR, which signi ﬁ cantly alters glucose and lipid homeostasis [50, 51].”
Acute Effects of Dietary Protein Consumption on the Postprandial Metabolic Response, Amino Acid Levels and Circulating MicroRNAs in Patients with Obesity and Insulin Resistance
Hernández-Gómez, K. G., Velázquez‐Villegas, L. A., Granados‐Portillo, O., Ávila-Nava, A., González-Salazar, L. E., Serralde-Zúñiga, A. E., Palacios‐González, B., Pichardo‐Ontiveros, E., Guizar-Heredia, R., López‐Barradas, A. M., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147716 · Cited by 8
“However, these regulatory mechanisms are altered in the insulin-resistant state [27–30].”
Background
Allantoin reduces glucotoxicity and lipotoxicity in a type 2 diabetes rat model by modulating the PI3K and MAPK signaling pathways
Zhao, Y., Qiao, M., Wang, X.-M., Luo, X., Yang, J.-H., & Hu, J.-P. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e34716 · Cited by 8
Small molecules targeting selective PCK1 and PGC-1α lysine acetylation cause anti-diabetic action through increased lactate oxidation
Mutlu, B., Sharabi, K., Sohn, J. H., Yuan, B., Latorre‐Muro, P., Qin, X., Yook, J.-S., Lin, H., Yu, D., Camporez, J. P., et al. (2024) · Cell chemical biology · doi:10.1016/j.chembiol.2024.09.001 · Cited by 8
Polyherbal formulation improves glucose-lipid metabolism and prevent hepatotoxicity in streptozotocin-induced diabetic rats: Plausible role of IRS-PI3K-Akt-GLUT2 signaling
Sharma, M., Haye, A., Ansari, M., Saini, A., Ahmed, Z., Munjal, K., & Shamsi, Y. (2022) · Pharmacognosy Magazine · doi:10.4103/pm.pm_318_21 · Cited by 7
Effect of Different Dietary Zinc Sources on Growth, Element Deposition, Antioxidation, Lipid Metabolism, and Related Gene Expression in Hybrid Grouper (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatus)
Wang, R., Ren, Y., Javed, H. U., Luo, J., Zhou, M., & Shu, X. (2022) · Aquaculture Nutrition · doi:10.1155/2022/8371440 · Cited by 7
“Insulin resistance does not prevent the liver from producing glucose, making it easier to accumulate lipids in the liver, resulting in elevated blood glucose and triglycerides, which are linked to the development of fatty liver [50, 51].”
Background
Multi-layered proteomics identifies insulin-induced upregulation of the EphA2 receptor via the ERK pathway which is dependent on low IGF1R level
Jørgensen, S. H., Emdal, K. B., Pedersen, A.-K., Axelsen, L. N., Kildegaard, H. F., Demozay, D., Pedersen, T. Å., Grønborg, M., Slaaby, R., Nielsen, P. K., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-77817-5 · Cited by 7
Non-invasive identification of steatohepatitis in patients with MASLD using a sterol and lipidomic signature
Pebriana, R. B., Chen, T., Derks, R. J. E., Blomberg, N., Grefhorst, A., Mohammed, Y., Nieuwdorp, M., Verheij, J., Doukas, M., Rensen, P. C. N., et al. (2025) · Journal of Lipid Research · doi:10.1016/j.jlr.2025.100845 · Cited by 6
“Abdominal, particularly visceral, obesity is strongly associated with MASLD, caused by a high flux of free fatty acids from insulin-resistant adipocytes to the liver in combination with increased hepatic lipogenesis driven by hyperinsulinemia (2, 3).”
Close multilevel links between metabolic dysfunction-associated steatotic liver disease and type 2 diabetes mellitus
Holleboom, A. G., Francque, S., Cusi, K. J., & Caussy, C. (2025) · Metabolism Open · doi:10.1016/j.metop.2025.100424 · Cited by 8
“In conjunction with the occurrence of steatosis, hepatocytes themselves become resistant to insulin due to actions of lipotoxic subspecies, especially diacylglycerol (DAG) [49].”
Low, non-psychedelic doses of psilocybin as a novel treatment for MASLD, obesity and type 2 diabetes via 5-HT2B receptor-dependent mechanisms
Colognesi, M., Gabbia, D., Signor, A., Sarill, M., Centofanti, L., Rinaldi, A., Cascione, L., Nunziata, S., Banzato, M., Mattarei, A., et al. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.108080 · Cited by 8
Sterol Regulatory Element-Binding Proteins and Metabolic Diseases: Mechanisms, Implications, and Therapeutic Strategies
Zhang, X., Zhang, K., Wang, Y., Fan, Q., Kan, C., Ma, Y., Sheng, S., Hou, N., & Sun, X. (2025) · Metabolic Syndrome and Related Disorders · doi:10.1177/15578518251407655 · Cited by 6
“40,41 In cases of insulin resistance, disrupted insulin signaling and reduced hepatocyte sensitivity lead to uncontrolled hepatic glucose production and hyperinsulinemia, further enhancing SREBP-1c-dependent adipogenesis.”
Cold exposure and human metabolism: A heterogeneous response across tissues and organs
Tetzlaff, E. J., Hancock, C. L., Waddell, L., Gagnon, S. S., Mäkelä, K. A., Karhu, T., Peltonen, J. E., Herzig, K., & Gagnon, D. D. (2026) · Temperature · doi:10.1080/23328940.2025.2599582 · Cited by 6
“On the other hand, insulin inhibits lipolysis and glucagon secretion [240], fatty acid oxidation, gluconeogenesis, synthesis but increases de novo lipogenesis, triglyceride esterification, triglyceride secretion [242], glycolysis and glycogen synthesis [243].”
Impaired glucose metabolism reduces the neuroprotective action of adipocytokines in cognitively normal older adults with insulin resistance
Lopez-Vilaret, K. M., Cantero, J. L., Fernandez-Alvarez, M., Calero, M., Calero, O., Lindı́n, M., Zurrón, M., Dı́az, F., & Atienza, M. (2021) · Aging · doi:10.18632/aging.203668 · Cited by 6
“During the progression of IR, insulin fails to suppress hepatic glucose production, but paradoxically accelerates lipid synthesis, leading to hyperglycemia and hypertriglyceridemia [55].”
Background
Global-run on sequencing identifies Gm11967 as an Akt-dependent long noncoding RNA involved in insulin sensitivity
Santoleri, D., Lim, H., Emmett, M. J., Stoute, J., Gavin, M. J., Sostre‐Colón, J., Uehara, K., Welles, J. E., Liu, K. F., Lazar, M. A., et al. (2022) · iScience · doi:10.1016/j.isci.2022.104410 · Cited by 5
“The serine/threonine kinase Akt plays a central role in the hepatic response to insulin, promoting hepatic glucose utilization, glycogen synthesis, and lipogenesis while simultaneously suppressing gluconeogenesis (Titchenell et al., 2017; Santoleri and Titchenell, 2018).”
Background
Iridoid glycoside isolated from Wendlandia glabrata and the role of its enriched fraction in regulating AMPK/PEPCK/G6Pase signaling pathway of hepatic gluconeogenesis
Sarma, P., Bharadwaj, S., Swargiary, D., Ahmed, S. A., Sheikh, Y., Barge, S., Manna, P., Talukdar, N. C., Bora, J. J., & Borah, J. C. (2022) · New Journal of Chemistry · doi:10.1039/d1nj05856h · Cited by 6
The Extent of Insulin Resistance in Patients That Cleared Viral Hepatitis C Infection and the Role of Pre-Existent Type 2 Diabetes Mellitus: A Meta-Analysis
Popescu, M. S., Drocaș, A. I., Osman, A., Firu, D.-M., Pădureanu, V., Mărginean, C. M., Pîrvu, D.-C., Mitruţ, R., Mărgăritescu, D. N., Radu, A., et al. (2022) · Reports — Medical Cases Images and Videos · doi:10.3390/reports5040042 · Cited by 6
“According to clinical definitions, IR is a disease that makes cells less responsive to an established amount of insulin, necessitating larger doses of insulin to produce the same cellular response [4].”
Background
Coagulation Factor VII Fine-tunes Hepatic Steatosis by Blocking AKT-CD36–Mediated Fatty Acid Uptake
Zhang, Y., Jiang, Q., Liang, X., Qian, Q., Xiong, J., Liu, C., Xu, J., Wang, N., Xu, Y., Zhou, P., et al. (2024) · Diabetes · doi:10.2337/db23-0814 · Cited by 6
Genetic determinants of obesity heterogeneity in type II diabetes
Khorami, S. A. H., Mutalib, M. S. A., Shiraz, M. F., Abdullah, J. A., Rejali, Z., Ali, R. M., & Khaza’ai, H. (2020) · Nutrition & Metabolism · doi:10.1186/s12986-020-00476-6 · Cited by 9
Genetic underpinnnings of type 2 diabetes
Shah, A., Bush, C. O., & Perry, R. J. (2025) · Advances in genetics · doi:10.1016/bs.adgen.2024.12.001 · Cited by 6
The association of the metabolic score for insulin resistance and metabolic dysfunction-related steatosis liver disease: a population-based observational study
Zou, H., Ma, X., Wen, P., & Xie, Y. (2025) · European journal of medical research · doi:10.1186/s40001-025-02936-2 · Cited by 7
“…[12], and its pathogenesis is not completely clear, and the more widely accepted theories are the “double-hit” theory and the “multiple-hit” theory [13, 14], but whether it is the"double-hit"or “multiple-hit” theory, insulin resistance (IR) is an essential part of the development of MASLD [15–20].”
Flavone C-Glycosides from Dianthus superbus L. Attenuate Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) via Multi-Pathway Regulations
Chu, M., Tong, Y., Zhang, L., Zhang, Y. X., Dang, J., & Li, G. (2025) · Nutrients · doi:10.3390/nu17152456 · Cited by 5
The pathogenesis of metabolic dysfunction-associated steatotic liver disease and nucleoside reverse transcriptase inhibitors (NRTIs) -based HIV-antiretroviral regimens: A comprehensive narrative review
Horn, M., Gumede, N. M., & Gamede, M. W. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118633 · Cited by 5
A new liver-targeted agonist of thyroid hormone receptor beta resmetirom in treating MASLD/MASH: From mechanism to therapy
Liu, M., Ma, Y., Cheang, W. S., Su, Z., & Xu, S. (2026) · Molecular Therapy · doi:10.1016/j.ymthe.2026.04.011 · Cited by 8
The effects of voluntary wheel running during weight-loss on biomarkers of hepatic lipid metabolism and inflammation in C57Bl/6J mice
Wooten, J. S., Poole, K. E., Harris, M. P., Guilford, B. L., Schaller, M. L., Umbaugh, D. S., & Seija, A. (2022) · Current Research in Physiology · doi:10.1016/j.crphys.2022.01.003 · Cited by 5
“The sources of excess free fatty acids that make up the hepatic triglyceride lipid pool includes increased uptake of circulating free fatty acids from adipose tissue lipolysis, de novo lipogenesis, and dietary lipids (Donnelly et al., 2005; Santoleri and Titchenell, 2019).”
Background

Authors: Santoleri, D., & Titchenell, P. M.
Affiliations: University of Pennsylvania (US)
Corresponding author: Titchenell, Paul M.
ORCID: Santoleri, Dominic
Titchenell, Paul M.
Venue: Cellular and Molecular Gastroenterology and Hepatology
Publisher: Elsevier BV
Published: 2019
Volume: 7
Issue: 2
Pages: 447-456
ISSN: 2352-345X (ISSN-L)
DOI: 10.1016/j.jcmgh.2018.10.016
PMC: PMC6369222
OpenAlex: W2899043265
Cited by: 336
References: 102
Citations by year: 2026: 35 · 2025: 57 · 2024: 61 · 2023: 63 · 2022: 51 · 2021: 40 · 2020: 24 · 2019: 5
FWCI: 2.57
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: Cellular and Molecular Gastroenterology and Hepatology (publishedVersion, cc-by-nc-nd)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institutes of Health (K01 DK111715, P30 DK19525)
Topics: Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: hepatic insulin resistance, insulin signaling, hepatic glucose production, hepatic lipid synthesis, hypertriglyceridemia, hyperglycemia, type 2 diabetes, obesity, glucose metabolism, lipid metabolism
MeSH terms: Animals, Humans, Insulin, Insulin Resistance, Liver, Models, Biological, Signal Transduction, Lipid Metabolism

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Resolving the Paradox of Hepatic Insulin Resistance

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