{"id":5229,"date":"2013-06-27T10:44:11","date_gmt":"2013-06-27T01:44:11","guid":{"rendered":"http:\/\/mus.brc.riken.jp:7301\/?page_id=5229"},"modified":"2021-04-07T14:19:01","modified_gmt":"2021-04-07T05:19:01","slug":"nov_2012_mm","status":"publish","type":"page","link":"http:\/\/mus.brc.riken.jp\/ja\/mouse_of_month\/nov_2012_mm","title":{"rendered":"November 2012 Metabolic impact of glucagon deficiency"},"content":{"rendered":"

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Metabolic impact of glucagon deficiency<\/em><\/strong><\/h2>\n
\u00a0\u00a0B6.129S6-Gcg<\/em>tm1Yhys<\/sup> RBRC02831<\/a><\/h5>\n
\"Metabolic
Courtesy of Dr. Yoshitaka Hayashi, Nagoya University<\/figcaption><\/figure>\n

Fluorescent images of pancreas (upper panels) and microscopic images of islets (lower panels) in\u00a0Gcggfp\/+<\/sup><\/em>\u00a0and\u00a0Gcggfp\/gfp<\/sup><\/em>\u00a0mice.<\/strong>In heterozygous\u00a0Gcggfp\/+<\/sup><\/em>\u00a0mice, green fluorescent protein (GFP) is expressed in islet \u03b1-cells (gfp\/+<\/em>). In homozygous\u00a0Gcggfp\/gfp<\/sup><\/em>\u00a0mice lacking all the peptides derived from proglucagon, islet number is increased and \u03b1-cells, which express GFP but not glucagon, display marked hyperplasia. The two left images in the top lane,\u00a0gfp\/+<\/em>\u00a0and\u00a0gfp\/gfp<\/em>, were obtained using a VB-G25 epifluorescent microscope system under the same condition (2-s exposure), while the right image (gfp\/gfp<\/em>*<\/sup>) was obtained with a 0.02-s exposure. S: spleen; D: duodenum. The layer of GFP-positive cells is thickened in the\u00a0Gcggfp\/gfp<\/sup><\/em>\u00a0mouse islet (gfp\/gfp<\/em>\u00a0in the lower lane), compared with that in the\u00a0Gcggfp\/+<\/sup><\/em>\u00a0mouse islet (gfp\/+<\/em>). GFP is shown in green and insulin is shown in red.
\nScale: 100 \u03bcm.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

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Proglucagon, which is encoded by the glucagon gene Gcg<\/em>, is a precursor of several peptide hormones, including glucagon and glucagon-like peptide 1 (GLP-1). Glucagon is produced in pancreatic islet \u03b1-cells through the cleavage of proglucagon by prohormone convertase 2 (Pcsk2), and it stimulates hepatic glycogenolysis and gluconeogenesis in order to increase blood glucose levels. GLP-1 is produced mainly in intestinal L cells and stimulates insulin secretion to lower blood glucose levels.<\/p>\n<\/div>\n

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Dr. Hayashi and colleagues have recently established mice lacking Gcg<\/em> by replacing Gcg<\/em> with cDNA for GFP (Gcggfp\/+<\/sup><\/em> mice) [1]. The serum concentration of insulin and the expression of enzymes involved in the conversion of amino acids to metabolites in the liver are reduced in Gcggfp\/gfp<\/sup><\/em> mice [2]. Pregnant Gcggfp\/gfp<\/sup><\/em> females show high blood glucose levels in late gestation, a decreased pregnancy rate, and smaller litter size [3]. Conversely, blood glucose levels in non-pregnant Gcggfp\/gfp<\/sup><\/em> mice are not significantly different from those in wild-type mice. The metabolic impact of proglucagon deficiency may be ameliorated by lower plasma insulin levels and by glucagon-independent mechanisms that maintain gluconeogenesis. Indeed, Pcsk2 knockout mice and glucagon receptor knockout mice both exhibit increased production of GLP-1, which is absent in Gcggfp\/gfp<\/sup><\/em> mice [4]. Gcggfp\/gfp<\/sup><\/em> mice provide the opportunity to clarify the development, differentiation, and function of Gcg<\/em>-expressing cells, as well as the physiological and pathological roles of glucagon in metabolism.<\/p>\n<\/div>\n\n\n\n
Depositor<\/td>\n:<\/td>\nDr. Yoshitaka Hayashi
\nDepartment of Genetics, Research Institute of Environmental Medicine
\nNagoya University<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n\n\n\n
References<\/td>\n:<\/td>\n[1]<\/td>\nHayashi Y, Yamamoto M, Mizoguchi H, Watanabe C, Ito R, Yamamoto S, Sun XY, Murata Y. Mice deficient for glucagon gene-derived peptides display normoglycemia and hyperplasia of islet alpha-cells but not of intestinal L-cells. Mol Endocrinol; 23(12):1990-9, 2009<\/a>.<\/td>\n<\/tr>\n
[2]<\/td>\nWatanabe C, Seino Y, Miyahira H, Yamamoto M, Fukami A, Ozaki N, Takagishi Y, Sato J, Fukuwatari T, Shibata K, Oiso Y, Murata Y, Hayashi Y. Remodeling of hepatic metabolism and hyperaminoacidemia in mice deficient in proglucagon-derived peptides. Diabetes; 61(1):74-84, 2012<\/a>.<\/td>\n<\/tr>\n
[3]<\/td>\nSugiyama C, Yamamoto M, Kotani T, Kikkawa F, Murata Y, Hayashi Y. Fertility and pregnancy-associated beta-cell proliferation in mice deficient in proglucagon-derived peptides. PLoS One; 7(8):e43745, 2012<\/a>.<\/td>\n<\/tr>\n
[4]<\/td>\nHayashi Y. Metabolic impact of glucagon deficiency. Diabetes Obes Metab; 13 Suppl 1:151-7, 2011<\/a>.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

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Metabolic impact of glucagon deficiency \u00a0\u00a0B6.129S6-Gcgtm1Yhys RBRC02831 Fluorescent images of pancreas (upper panels) and microscopic images of islets (lower panels) in\u00a0Gcggfp\/+\u00a0and\u00a0Gcggfp\/gfp\u00a0mice.In […]<\/p>\n","protected":false},"author":8,"featured_media":0,"parent":198,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","_seopress_robots_follow":"","_seopress_robots_imageindex":"","_seopress_robots_snippet":"","_seopress_robots_primary_cat":"","_seopress_robots_breadcrumbs":"","_seopress_robots_freeze_modified_date":"","_seopress_robots_custom_modified_date":"","_seopress_robots_canonical":"","_seopress_social_fb_title":"","_seopress_social_fb_desc":"","_seopress_social_fb_img":"","_seopress_social_fb_img_attachment_id":0,"_seopress_social_fb_img_width":0,"_seopress_social_fb_img_height":0,"_seopress_social_twitter_title":"","_seopress_social_twitter_desc":"","_seopress_social_twitter_img":"","_seopress_social_twitter_img_attachment_id":0,"_seopress_social_twitter_img_width":0,"_seopress_social_twitter_img_height":0,"_seopress_redirections_value":"","_seopress_redirections_enabled":"","_seopress_redirections_enabled_regex":"","_seopress_redirections_logged_status":"","_seopress_redirections_param":"","_seopress_redirections_type":301,"_seopress_analysis_target_kw":"","footnotes":"","_wp_rev_ctl_limit":""},"class_list":["post-5229","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/pages\/5229","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/comments?post=5229"}],"version-history":[{"count":9,"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/pages\/5229\/revisions"}],"predecessor-version":[{"id":18165,"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/pages\/5229\/revisions\/18165"}],"up":[{"embeddable":true,"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/pages\/198"}],"wp:attachment":[{"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/media?parent=5229"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}