{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:21:57Z","timestamp":1761895317223,"version":"build-2065373602"},"reference-count":61,"publisher":"Wiley","issue":"s1","license":[{"start":{"date-parts":[[2011,8,8]],"date-time":"2011-08-08T00:00:00Z","timestamp":1312761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:p>\n                    In health, the pancreatic islet cells work as a network with highly co\u2010ordinated signals over time to balance glycaemia within a narrow range. In type 1 diabetes (T1DM), with autoimmune destruction of the\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010cells, lack of insulin is considered the primary abnormality and is the primary therapy target. However, replacing insulin alone does not achieve adequate glucose control and recent studies have focused on controlling the endogenous glucagon release as well. In T1DM, glucagon secretion is disordered but not absolutely deficient; it may be excessive postprandially yet it is characteristically insufficient and delayed in response to hypoglycaemia. We review our system\u2010level analysis of the pancreatic endocrine network mechanisms of glucagon counterregulation (GCR) and their dysregulation in T1DM and focus on possible use of\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010cell inhibitors (ACIs) to manipulate the glucagon axis to repair the defective GCR. Our results indicate that the GCR abnormalities are of \u2018network origin\u2019. The lack of\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010cell signalling is the primary deficiency that contributes to two separate network abnormalities: (i) absence of a\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010cell switch\u2010off trigger and (ii) increased intraislet basal glucagon. A strategy to repair these abnormalities with ACI is proposed, which could achieve better control of glycaemia with reduced hypoglycaemia risk.\n                  <\/jats:p>","DOI":"10.1111\/j.1463-1326.2011.01455.x","type":"journal-article","created":{"date-parts":[[2011,8,8]],"date-time":"2011-08-08T11:54:32Z","timestamp":1312804472000},"page":"133-143","source":"Crossref","is-referenced-by-count":14,"title":["Optimizing reduction in basal hyperglucagonaemia to repair defective glucagon counterregulation in insulin deficiency"],"prefix":"10.1111","volume":"13","author":[{"given":"L. S.","family":"Farhy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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