The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Insulin action in the brain contributes to glucose lowering during insulin treatment of diabetes
Open accessAbstract
To investigate the role of brain insulin action in the pathogenesis and treatment of diabetes, we asked whether neuronal insulin signaling is required for glucose-lowering during insulin treatment of diabetes. Hypothalamic signaling via the insulin receptor substrate-phosphatidylinositol 3-kinase (IRS-PI3K) pathway, a key intracellular mediator of insulin action, was reduced in rats with uncontrolled diabetes induced by streptozotocin (STZ-DM). Further, infusion of a PI3K inhibitor into the third cerebral ventricle of STZ-DM rats prior to peripheral insulin injection attenuated insulin-induced glucose lowering by approximately 35%-40% in both acute and chronic insulin treatment paradigms. Conversely, increased PI3K signaling induced by hypothalamic overexpression of either IRS-2 or protein kinase B (PKB, a key downstream mediator of PI3K action) enhanced the glycemic response to insulin by approximately 2-fold in STZ-DM rats. We conclude that hypothalamic insulin signaling via the IRS-PI3K pathway is a key determinant of the response to insulin in the management of uncontrolled diabetes.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Both, peripheral and central insulin signaling are impaired in obese or diabetic states.150, 151, 152, 153, 154”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [154]
Experimental — accuracy not yet measuredIn the citing paper
“increasing hypothalamic PI3K signaling, a major intracellular mediator of insulin action, by local overexpression of IRS-2 increases peripheral insulin sensitivity in rats with uDM induced by STZ (65).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [65]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Role of Brain Insulin Receptor in Control of Body Weight and Reproduction
Brüning, J. C., Gautam, D., Burks, D. J., Gillette, J., Schubert, M., Orban, P. C., Klein, R., Krone, W., Müller-Wieland, D., & Kahn, C. R. (2000) · Science · doi:10.1126/science.289.5487.2122 · Cited by 2,235
Flier, J. S. (2004) · Cell · doi:10.1016/s0092-8674(03)01081-x · Cited by 1,124
Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons
Woods, S. C., Lotter, E. C., McKay, L. D., & Porte, D. (1979) · Nature · doi:10.1038/282503a0 · Cited by 1,114
Hypothalamic insulin signaling is required for inhibition of glucose production
Obici, S., Zhang, B. B., Karkanias, G., & Rossetti, L. (2002) · Nature Medicine · doi:10.1038/nm1202-798 · Cited by 904
Diabetes, Obesity, and the Brain
Schwartz, M. W., & Porte, D. (2005) · Science · doi:10.1126/science.1104344 · Cited by 841
Self-citationInsulin in the Brain: A Hormonal Regulator of Energy Balance*
Schwartz, M. W., Figlewicz, D. P., Baskin, D. G., Woods, S. C., & Porte, D. (1992) · Endocrine Reviews · doi:10.1210/edrv-13-3-387 · Cited by 808
Self-citationDecreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats
Obici, S., Feng, Z., Karkanias, G., Baskin, D. G., & Rossetti, L. (2002) · Nature Neuroscience · doi:10.1038/nn0602-861 · Cited by 719
Central Administration of Oleic Acid Inhibits Glucose Production and Food Intake
Obici, S., Feng, Z., Morgan, K., Stein, D., Karkanias, G., & Rossetti, L. (2002) · Diabetes · doi:10.2337/diabetes.51.2.271 · Cited by 654
Hypothalamic KATP channels control hepatic glucose production
Pocai, A., Lam, T. K. T., Gutierrez-Juarez, R., Obici, S., Schwartz, G. J., Bryan, J., Aguilar-Bryan, L., & Rossetti, L. (2005) · Nature · doi:10.1038/nature03439 · Cited by 645
Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats
Obici, S., Feng, Z., Karkanias, G. B., et al. (2002) · Nature Neuroscience · doi:10.1038/nn861 · Cited by 572
Cited by
Sorted by citations
The integrative biology of type 2 diabetes
Roden, M., & Shulman, G. I. (2019) · Nature · doi:10.1038/s41586-019-1797-8 · Cited by 1,167
Pancreatic regulation of glucose homeostasis.
Röder, P. V., Wu, B., Liu, Y., & Han, W. (2016) · Experimental & Molecular Medicine · doi:10.1038/emm.2016.6 · Cited by 985
Holland, W. L., Bikman, B. T., Wang, L.-P., Yuguang, G., Sargent, K. M., Bulchand, S., Knotts, T. A., Shui, G., Clegg, D. J., Wenk, M. R., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci43378 · Cited by 705
Insulin Action in AgRP-Expressing Neurons Is Required for Suppression of Hepatic Glucose Production
Könner, A. C., Janoschek, R., Plum, L., Jordan, S. D., Rother, E., Ma, X., Xu, C., Enriori, P., Hampel, B., Barsh, G. S., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.004 · Cited by 695
A Ceramide-Centric View of Insulin Resistance
Chavez, J. A., & Summers, S. A. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.002 · Cited by 637
Metadata
- Authors
- Gelling, R. W., Morton, G. J., Morrison, C. D., Niswender, K. D., Myers, M. G., Rhodes, C. J., & Schwartz, M. W.
- Affiliations
- University of Washington (US)
- University of Michigan (US)
- Corresponding author
- Schwartz, Michael W.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 3
- Issue
- 1
- Pages
- 67-73
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2052985185
- Cited by
- 169
- References
- 27
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 4 · 2019: 10 · 2018: 8 · 2017: 9 · 2016: 9 · 2015: 12 · 2014: 8 · 2013: 9 · 2012: 18
- FWCI
- 5.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Washington
- National Institutes of Health (2r01dk012829-36, DK‐12829, NS32273)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 12829, R01DK052989, DK68340, DK-52989)
- National Institute of Neurological Disorders and Stroke (NS-32273)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- hypothalamus, insulin signaling, insulin receptor substrate, phosphatidylinositol 3-kinase, Akt, insulin receptor substrate 2, streptozotocin-induced diabetes, insulin resistance, glucose homeostasis
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Animals, Blood Glucose, Brain, Chromones, Diabetes Mellitus, Experimental, Insulin, Male, Morpholines, Nerve Tissue Proteins, Rats, Sprague-Dawley, Rats
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
