{"doi":"10.2337/db10-0728","title":"Insulin Reciprocally Regulates Glucagon Secretion in Humans","abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE</jats:title>\n                  <jats:p>We tested the hypothesis that an increase in insulin per se, i.e., in the absence of zinc, suppresses glucagon secretion during euglycemia and that a decrease in insulin per se stimulates glucagon secretion during hypoglycemia in humans.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS</jats:title>\n                  <jats:p>We measured plasma glucagon concentrations in patients with type 1 diabetes infused with the zinc-free insulin glulisine on three occasions. Glulisine was infused with clamped euglycemia (∼95 mg/dl [5.3 mmol/l]) from 0 to 60 min on all three occasions. Then, glulisine was discontinued with clamped euglycemia or with clamped hypoglycemia (∼55 mg/dl [3.0 mmol/l]) or continued with clamped hypoglycemia from 60 to 180 min.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS</jats:title>\n                  <jats:p>Plasma glucagon concentrations were suppressed by −13 ± 3, −9 ± 3, and −12 ± 2 pg/ml (−3.7 ± 0.9, −2.6 ± 0.9, and −3.4 ± 0.6 pmol/l), respectively, (all P &amp;lt; 0.01) during zinc-free hyperinsulinemic euglycemia over the first 60 min. Glucagon levels remained suppressed following a decrease in zinc-free insulin with euglycemia (−14 ± 3 pg/ml [−4.0 ± 0.9 pmol/l]) and during sustained hyperinsulinemia with hypoglycemia (−14 ± 2 pg/ml [−4.0 ± 0.6 pmol/l]) but increased to −3 ± 3 pg/ml (−0.9 ± 0.9 pmol/l) (P &amp;lt; 0.01) following a decrease in zinc-free insulin with hypoglycemia over the next 120 min.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS</jats:title>\n                  <jats:p>These data indicate that an increase in insulin per se suppresses glucagon secretion and a decrease in insulin per se, in concert with a low glucose concentration, stimulates glucagon secretion. Thus, they document that insulin is a β-cell secretory product that, in concert with glucose and among other signals, reciprocally regulates α-cell glucagon secretion in humans.</jats:p>\n               </jats:sec>","journal":"Diabetes","year":2010,"id":603804,"datarank":0.7423139835567254,"base_score":4.948759890378168,"endowment":4.948759890378168,"self_citation_contribution":0.7423139835567254,"citation_network_contribution":0.0,"self_endowment_contribution":0.7423139835567254,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":140,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1548956,"name":"Philip E. Cryer","orcid":null,"position":1,"is_corresponding":false},{"id":1548955,"name":"Benjamin A. Cooperberg","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-29T22:45:27.440116Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}