Hormonal
Central brain GLP-1 receptor activation during hyperglycemia induces muscle insulin resistance and increases insulin secretion, thereby redirecting glucose flux to favor hepatic glycogen storage over muscle glycogen storage.
Brain GLP-1 signaling acts as a switch during high blood sugar states to prioritize liver glycogen storage over muscle storage. This is achieved by increasing insulin secretion and inducing temporary muscle insulin resistance. This mechanism prepares the body for the next fasting period by ensuring liver glycogen is replenished. This effect is specific to hyperglycemic conditions and does not occur during normal blood sugar levels.
Our data show that during hyperglycemia, brain GLP-1 inhibited muscle glucose utilization and increased insulin secretion to favor hepatic glycogen stores, preparing efficiently for the next fasting state.
Why this rating
Robust mechanistic evidence using multiple mouse models (WT, KO, MIRKO) and clamps, but results are from animal models.
Source
Brain glucagon-like peptide-1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage
Claude Knauf · Journal of Clinical Investigation · 2005
DOI 10.1172/jci25764
More from this paper
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
This is one finding among thousands. Every one is graded and traced to its source, so you can see what the evidence actually supports. Browse the research →