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Property "Has-20abstract" (as page type) with input value "Insulin-20is-20critical-20for-20glucose-20homeostasis,-20and-20insulin-20deficiency-20or-20resistance-20leads-20to-20the-20development-20of-20diabetes.-20Recent-20evidence-20suggests-20that-20diabetes-20can-20be-20remitted-20independent-20of-20insulin.-20However,-20the-20underlying-20mechanism-20remains-20largely-20elusive.-20In-20this-20study,-20we-20utilized-20metabolic-20surgery-20as-20a-20tool-20to-20identify-20the-20non-2Dinsulin-20determinant-20mechanism.-20Here,-20we-20report-20that-20the-20most-20common-20metabolic-20surgery,-20Roux-2Den-2DY-20gastric-20bypass-20(RYGB),-20reduced-20insulin-20production-20but-20persistently-20maintained-20euglycemia-20in-20healthy-20Sprague-2DDawley-20(SD)-20rats-20and-20C57-20mice.-20This-20reduction-20in-20insulin-20production-20was-20associated-20with-20RYGB-2Dmediated-20inhibition-20of-20pancreatic-20preproinsulin-20and-20polypyrimidine-20tract-2Dbinding-20protein-201.-20In-20addition,-20RYGB-20also-20weakened-20insulin-20sensitivity-20that-20was-20evaluated-20by-20hyperinsulinemic-2Deuglycemic-20clamp-20test-20and-20downregulated-20signaling-20pathways-20in-20insulin-2Dsensitive-20tissues.-20The-20mechanistic-20evidence-20suggests-20that-20RYGB-20predominately-20shifted-20the-20metabolic-20profile-20from-20glucose-20utilization-20to-20fatty-20acid-20oxidation,-20enhanced-20the-20energy-20expenditure-20and-20activated-20multiple-20metabolic-20pathways-20through-20reducing-20gut-20energy-20uptake.-20Importantly,-20the-20unique-20effect-20of-20RYGB-20was-20extended-20to-20rats-20with-20islet-20disruption-20and-20patients-20with-20type-202-20diabetes.-20These-20results-20demonstrate-20that-20compulsory-20rearrangement-20of-20the-20gastrointestinal-20tract-20can-20initiate-20non-2Dinsulin-20determinant-20pathways-20to-20maintain-20glucose-20homeostasis.-20Based-20on-20the-20principle-20of-20RYGB-20action,-20the-20development-20of-20a-20noninvasive-20intervention-20of-20the-20gastrointestinal-20tract-20is-20a-20promising-20therapeutic-20route-20to-20combat-20disorders-20characterized-20by-20energy-20metabolism-20dysregulation." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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