Activation of central lactate metabolism lowers glucose production in uncontrolled diabetes and diet-induced insulin resistance.
Abstract
OBJECTIVE: Hypothalamic lactate metabolism lowers hepatic glucose production and plasma glucose levels in normal rodents. However, it remains unknown whether activation of hypothalamic lactate metabolism lowers glucose production and plasma glucose levels in rodents with diabetes and obesity. RESEARCH DESIGN AND METHODS: We performed intracerebroventricular (ICV) administration of lactate to enhance central lactate metabolism in 1) early-onset streptozotocin-induced uncontrolled diabetic rodents, 2) experimentally induced hypoinsulinemic normal rodents, and 3) early-onset diet-induced insulin-resistant rodents. Tracer-dilution methodology was used to assess the impact of ICV lactate on the rate of glucose production in all three models. RESULTS: We first report that in the absence of insulin treatment, ICV lactate administration lowered glucose production and glucose levels in rodents with uncontrolled diabetes. Second, ICV lactate administration lowered glucose production and glucose levels in normal rodents with experimentally induced hypoinsulinemia. Third, and finally, ICV lactate administration lowered glucose production in normal rodents with diet-induced insulin resistance. CONCLUSIONS: Central lactate metabolism lowered glucose production in uncontrolled diabetic and normal rodents with hypoinsulinemia and in rodents with diet-induced insulin resistance. These data suggest that insulin signaling is not required for central lactate to lower glucose production and that the activation of hypothalamic lactate metabolism could consequently bypass insulin resistance and lower glucose levels in early-onset diabetes and obesity.
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CNS leptin reduces HGP independent of insulin.
“constituting direct evidence of a brain mechanism for reducing HGP independent of insulin (33).”
From Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia (2011) · cites this paper as [33]
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- Authors
- Chari, M., Lam, C. K. L., Wang, P. Y. T., & Lam, T. K. T.
- Affiliations
- University Health Network (CA)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2008-04-01
- Volume
- 57
- Issue
- 4
- Pages
- 836-840
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2099584401
- Cited by
- 53
- References
- 15
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 1 · 2014: 1 · 2013: 5 · 2012: 2
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- hypothalamus, hepatic glucose production, plasma glucose, uncontrolled diabetes, insulin resistance, hypoinsulinemia, streptozotocin-induced diabetes, diet-induced insulin resistance, obesity, insulin signaling
- MeSH terms
- Animals, Blood Glucose, Energy Intake, Diabetes Mellitus, Experimental, Dietary Fats, Glucose, Infusions, Intravenous, Insulin, Insulin Resistance, Lactates, Male, Rats, Sprague-Dawley, Rats
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