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Therefore, we investigated whether EA at ST25 exerts any beneficial effects on insulin resistance (IR), inflammation severity, and pancreatic<jats:italic>\u03b2<\/jats:italic>cell function via the PINS in a rat model of a high-fat diet-streptozotocin (HFD\/STZ)-induced diabetes. To this end, Sprague Dawley rats were fed with HFD to induce IR, followed by STZ (35 mg\/kg, i.p.) injection to establish the T2DM model. After hyperglycemia was confirmed as fasting glucose level &gt; 16.7 mmol\/L, the rats were treated with EA (2 mA, 2\/15 Hz) for the next 28 days. Model rats showed increased serum glucose, insulin, IR, and TNF-<jats:italic>\u03b1<\/jats:italic>levels with a concomitant decrease in<jats:italic>\u03b2<\/jats:italic>cell function. Microscopy examination of the pancreas revealed pathological changes in islets, which reverted to near-normal levels after EA at ST25. EA improved islet cell morphology by increasing islet area and reducing vacuolation. EA at ST25 decreased transient receptor potential vanilloid 1 (TRPV1) and increased substance P (SP) and calcitonin gene-related peptide (CGRP) expression. Subsequently, insulin secretion decreased and impaired pancreatic endocrine function was restored through the TRPV1 channel (SP\/CGRP)-insulin circuit. EA increased choline acetyltransferase and neuropeptide Y expression and controlled inflammation. It also enhanced the cocaine and amphetamine-regulated transcript prepropeptide expression and promoted glucagon-like peptide-1 secretion. Additionally, the electrophysiological activity of PINS during acupuncture (2.71 \u00b1 1.72 Hz) was significantly increased compared to the pre-acupuncture frequency (0.32 \u00b1 0.37 Hz,<jats:italic>P<\/jats:italic>&lt; 0.05). Thus, our study demonstrated the beneficial effect of EA on<jats:italic>\u03b2<\/jats:italic>cell dysfunction via the PINS in rat models of HFD-STZ-induced T2DM.<\/jats:p>","DOI":"10.1007\/s12035-021-02609-1","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T16:51:17Z","timestamp":1636563077000},"page":"703-716","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Hypoglycemic Effect of Electroacupuncture at ST25 Through Neural Regulation of the Pancreatic Intrinsic Nervous System"],"prefix":"10.1007","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0089-0712","authenticated-orcid":false,"given":"Tiancheng","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9179-2618","authenticated-orcid":false,"given":"Zhi","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0451-184X","authenticated-orcid":false,"given":"Yun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8635-4659","authenticated-orcid":false,"given":"Mengjiang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1497-5971","authenticated-orcid":false,"given":"Meirong","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8814-6180","authenticated-orcid":false,"given":"Qian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0408-2045","authenticated-orcid":false,"given":"Youbing","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4006-3009","authenticated-orcid":false,"given":"Bin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"2609_CR1","doi-asserted-by":"crossref","first-page":"m997","DOI":"10.1136\/bmj.m997","volume":"369","author":"Y Li","year":"2020","unstructured":"Li Y, Teng D, Shi X, Qin G, Qin Y, Quan H et al (2020) Prevalence of diabetes recorded in mainland China using 2018 diagnostic criteria from the American Diabetes Association: national cross sectional study. 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