{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T03:17:39Z","timestamp":1783480659022,"version":"3.55.0"},"reference-count":112,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2016,4,12]],"date-time":"2016-04-12T00:00:00Z","timestamp":1460419200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>A computer model designed to simulate integrated glucose-dependent changes in splanchnic blood flow with small intestinal glucose absorption, hormonal and incretin circulation and hepatic and systemic metabolism in health and metabolic diseases e.g. non-alcoholic fatty liver disease, (NAFLD), non-alcoholic steatohepatitis, (NASH) and type 2 diabetes mellitus, (T2DM) demonstrates how when glucagon-like peptide-1, (GLP-1) is synchronously released into the splanchnic blood during intestinal glucose absorption, it stimulates superior mesenteric arterial (SMA) blood flow and by increasing passive intestinal glucose absorption, harmonizes absorption with its distribution and metabolism. GLP-1 also synergises insulin-dependent net hepatic glucose uptake (NHGU). When GLP-1 secretion is deficient post-prandial SMA blood flow is not increased and as NHGU is also reduced, hyperglycaemia follows. Portal venous glucose concentration is also raised, thereby retarding the passive component of intestinal glucose absorption.\u00a0\u00a0<\/ns4:p>\n                  <ns4:p>Increased pre-hepatic sinusoidal resistance combined with portal hypertension leading to opening of intrahepatic portosystemic collateral vessels are NASH-related mechanical defects that alter the balance between splanchnic and systemic distributions of glucose, hormones and incretins.The model reveals the latent contribution of portosystemic shunting in development of metabolic disease. This diverts splanchnic blood content away from the hepatic sinuses to the systemic circulation, particularly during the glucose absorptive phase of digestion, resulting in inappropriate increases in insulin-dependent systemic glucose metabolism.\u00a0 This hastens onset of hypoglycaemia and thence hyperglucagonaemia. The model reveals that low rates of GLP-1 secretion, frequently associated with T2DM and NASH, may be also be caused by splanchnic hypoglycaemia, rather than to intrinsic loss of incretin secretory capacity. These findings may have therapeutic implications on GLP-1 agonist or glucagon antagonist usage.<\/ns4:p>","DOI":"10.12688\/f1000research.8299.1","type":"journal-article","created":{"date-parts":[[2016,4,12]],"date-time":"2016-04-12T07:55:04Z","timestamp":1460447704000},"page":"647","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["A computer model simulating human glucose absorption and metabolism in health and metabolic disease states"],"prefix":"10.12688","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8783-390X","authenticated-orcid":false,"given":"Richard J.","family":"Naftalin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2016,4,12]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"733-794","DOI":"10.1152\/physrev.00055.2009","article-title":"Biology of human sodium glucose transporters.","volume":"91","author":"E Wright","year":"2011","journal-title":"Physiol Rev."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"585-587","DOI":"10.1136\/gut.46.5.585","article-title":"The molecular and genetic base of congenital transport defects.","volume":"46","author":"J Desjeux","year":"2000","journal-title":"Gut."},{"key":"ref-3","first-page":"G879-G882","article-title":"Genetic disorders of membrane transport I. 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