Parental Diabetes: The Akita Mouse as a Model of the Effects of Maternal and Paternal Hyperglycemia in Wildtype Offspring
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{"title"=>"Parental Diabetes: The Akita Mouse as a Model of the Effects of Maternal and Paternal Hyperglycemia in Wildtype Offspring", "type"=>"journal", "authors"=>[{"first_name"=>"Corinna", "last_name"=>"Grasemann", "scopus_author_id"=>"16636221600"}, {"first_name"=>"Maureen J.", "last_name"=>"Devlin", "scopus_author_id"=>"7102114891"}, {"first_name"=>"Paulina A.", "last_name"=>"Rzeczkowska", "scopus_author_id"=>"24781204600"}, {"first_name"=>"Ralf", "last_name"=>"Herrmann", "scopus_author_id"=>"7402412002"}, {"first_name"=>"Bernhard", "last_name"=>"Horsthemke", "scopus_author_id"=>"56186820300"}, {"first_name"=>"Berthold P.", "last_name"=>"Hauffa", "scopus_author_id"=>"7004618117"}, {"first_name"=>"Marc", "last_name"=>"Grynpas", "scopus_author_id"=>"7005701646"}, {"first_name"=>"Christina", "last_name"=>"Alm", "scopus_author_id"=>"55757286500"}, {"first_name"=>"Mary L.", "last_name"=>"Bouxsein", "scopus_author_id"=>"7003791987"}, {"first_name"=>"Mark R.", "last_name"=>"Palmert", "scopus_author_id"=>"7003867085"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"doi"=>"10.1371/journal.pone.0050210", "issn"=>"19326203", "sgr"=>"84870307307", "pui"=>"366164723", "scopus"=>"2-s2.0-84870307307", "pmid"=>"23209676", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"8aa1f1b9-e2f0-3f1d-83d8-aa405d660835", "abstract"=>"AIM/HYPOTHESIS: Maternal diabetes and high-fat feeding during pregnancy have been linked to later life outcomes in offspring. To investigate the effects of both maternal and paternal hyperglycemia on offspring phenotypes, we utilized an autosomal dominant mouse model of diabetes (hypoinsulinemic hyperglycemia in Akita mice). We determined metabolic and skeletal phenotypes in wildtype offspring of Akita mothers and fathers.\\n\\nRESULTS: Both maternal and paternal diabetes resulted in phenotypic changes in wildtype offspring. Phenotypic changes were more pronounced in male offspring than in female offspring. Maternal hyperglycemia resulted in metabolic and skeletal phenotypes in male wildtype offspring. Decreased bodyweight and impaired glucose tolerance were observed as were reduced whole body bone mineral density and reduced trabecular bone mass. Phenotypic changes in offspring of diabetic fathers differed in effect size from changes in offspring of diabetic mothers. Male wildtype offspring developed a milder metabolic phenotype, but a more severe skeletal phenotype. Female wildtype offspring of diabetic fathers were least affected.\\n\\nCONCLUSIONS: Both maternal and paternal diabetes led to the development of metabolic and skeletal changes in wildtype offspring, with a greater effect of maternal diabetes on metabolic parameters and of paternal diabetes on skeletal development. The observed changes are unlikely to derive from Mendelian inheritance, since the investigated offspring did not inherit the Akita mutation. While fetal programming may explain the phenotypic changes in offspring exposed to maternal diabetes in-utero, the mechanism underlying the effect of paternal diabetes on wildtype offspring is unclear.", "link"=>"http://www.mendeley.com/research/parental-diabetes-akita-mouse-model-effects-maternal-paternal-hyperglycemia-wildtype-offspring", "reader_count"=>16, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>1, "Student > Master"=>2, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>1, "Student > Master"=>2, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/288183"], "description"=>"<div><h3>Aim/Hypothesis</h3><p>Maternal diabetes and high-fat feeding during pregnancy have been linked to later life outcomes in offspring. To investigate the effects of both maternal and paternal hyperglycemia on offspring phenotypes, we utilized an autosomal dominant mouse model of diabetes (hypoinsulinemic hyperglycemia in Akita mice). We determined metabolic and skeletal phenotypes in wildtype offspring of Akita mothers and fathers.</p> <h3>Results</h3><p>Both maternal and paternal diabetes resulted in phenotypic changes in wildtype offspring. Phenotypic changes were more pronounced in male offspring than in female offspring. Maternal hyperglycemia resulted in metabolic and skeletal phenotypes in male wildtype offspring. Decreased bodyweight and impaired glucose tolerance were observed as were reduced whole body bone mineral density and reduced trabecular bone mass.</p> <p>Phenotypic changes in offspring of diabetic fathers differed in effect size from changes in offspring of diabetic mothers. Male wildtype offspring developed a milder metabolic phenotype, but a more severe skeletal phenotype. Female wildtype offspring of diabetic fathers were least affected.</p> <h3>Conclusions</h3><p>Both maternal and paternal diabetes led to the development of metabolic and skeletal changes in wildtype offspring, with a greater effect of maternal diabetes on metabolic parameters and of paternal diabetes on skeletal development. The observed changes are unlikely to derive from Mendelian inheritance, since the investigated offspring did not inherit the Akita mutation. While fetal programming may explain the phenotypic changes in offspring exposed to maternal diabetes <em>in-utero</em>, the mechanism underlying the effect of paternal diabetes on wildtype offspring is unclear.</p> </div>", "links"=>[], "tags"=>["akita", "effects", "maternal", "paternal", "hyperglycemia", "wildtype", "offspring"], "article_id"=>116768, "categories"=>["Chemistry", "Physiology", "Genetics"], "users"=>["Corinna Grasemann", "Maureen J. Devlin", "Paulina A. Rzeczkowska", "Ralf Herrmann", "Bernhard Horsthemke", "Berthold P. Hauffa", "Marc Grynpas", "Christina Alm", "Mary L. Bouxsein", "Mark R. Palmert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050210", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Parental_Diabetes_The_Akita_Mouse_as_a_Model_of_the_Effects_of_Maternal_and_Paternal_Hyperglycemia_in_Wildtype_Offspring__/116768", "title"=>"Parental Diabetes: The Akita Mouse as a Model of the Effects of Maternal and Paternal Hyperglycemia in Wildtype Offspring", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-11-28 01:52:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/536145"], "description"=>"<p>P-values for influence of group (maternal diabetes/paternal diabetes/control), age and sex on phenotypic markers are provided, as well as p-values for interactions of group and age, age and sex, sex and group, sex and age are given. Cells with p<0.05 are highlighted.</p>", "links"=>[], "tags"=>["3-way"], "article_id"=>206633, "categories"=>["Chemistry", "Physiology", "Genetics"], "users"=>["Corinna Grasemann", "Maureen J. Devlin", "Paulina A. Rzeczkowska", "Ralf Herrmann", "Bernhard Horsthemke", "Berthold P. Hauffa", "Marc Grynpas", "Christina Alm", "Mary L. Bouxsein", "Mark R. Palmert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050210.t001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Results_3_way_ANOVA_/206633", "title"=>"Results 3-way ANOVA.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-11-28 01:50:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/535701"], "description"=>"<p>Boxplots showing the smallest observation (lower bar), lower and upper quartile (box), median (line in the box) and largest observation (upper bar) of fasted serum glucose in mmol/L in <b>a</b>) WT and Akita males (n = 26 WT, 8 Akita) and females (n = 22 WT, 19 Akita) prior to mating, <b>b</b>) WT and Akita females on day 17 of pregnancy and <b>c</b>) wildtype (n = 10) and heterozygous (Akita) pups (n = 7) <i>in-utero</i> on day 17 of pregnancy and WT pups (n = 5) from control breedings on day 17 of pregnancy. *** indicate p<0.001 <b>d</b>) Weight gain from weaning to 20 weeks of life for male and female offspring of maternal diabetes and controls (mean weight in g ± SEM, n 8–15 per group). Offspring of diabetic mothers weighed less from weaning (for males: 8.16+0.9 g vs. 8.75+0.8 g in controls and for females: 8.0+0.6 g vs 8.4+1.0 g in controls) to sacrifice.</p>", "links"=>[], "tags"=>["glucose"], "article_id"=>206188, "categories"=>["Chemistry", "Physiology", "Genetics"], "users"=>["Corinna Grasemann", "Maureen J. Devlin", "Paulina A. Rzeczkowska", "Ralf Herrmann", "Bernhard Horsthemke", "Berthold P. Hauffa", "Marc Grynpas", "Christina Alm", "Mary L. Bouxsein", "Mark R. Palmert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050210.g002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Premating_and_Pregnancy_Glucose_Values_/206188", "title"=>"Premating and Pregnancy Glucose Values.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-28 01:43:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/536188"], "description"=>"<p>Mean+SD and animal numbers (n) as well as numbers of pregnancies () are provided for male offspring at 14 and 26 weeks of age for phenotypic markers obtained in offspring of maternal diabetes, paternal diabetes and controls. Significant differences to control offspring (p<0.05) are highlighted in grey shaded boxes (*, p<0.05).</p><p>AUC: Area under the curve for glucose response after ipGTT, BMD: bone mineral density, BMC: bone mineral content, LBW: lean body weight, BFAT: body fat, Tb.Th.: trabecular thickness, Tb.N.: number of trabeculae, Cort. Area: Cortical area, BA/TA: Bone area/trabecular area, Cort. Th.: Cortical thickness.</p>", "links"=>[], "tags"=>["metabolic", "skeletal", "markers", "offspring", "separated"], "article_id"=>206669, "categories"=>["Chemistry", "Physiology", "Genetics"], "users"=>["Corinna Grasemann", "Maureen J. Devlin", "Paulina A. Rzeczkowska", "Ralf Herrmann", "Bernhard Horsthemke", "Berthold P. Hauffa", "Marc Grynpas", "Christina Alm", "Mary L. Bouxsein", "Mark R. Palmert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050210.t002", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phenotypic_results_for_metabolic_and_skeletal_markers_in_male_offspring_separated_by_age_and_group_/206669", "title"=>"Phenotypic results for metabolic and skeletal markers in male offspring separated by age and group.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-11-28 01:51:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/535872"], "description"=>"<p>Boxplots showing the smallest observation (lower bar), lower and upper quartile (box), median (line in the box) and largest observation (upper bar) of selected phenotypic markers: <b>a</b>) weight in g, <b>b</b>) fasted, glucose in mmol/L, <b>c</b>) AUC and <b>d</b>) fasted insulin (ng/ml) are given for male offspring of control breedings (open bars), paternal diabetes (longitudinal shading) and maternal diabetes (diagonal shading), at 14 and 26 weeks of age. Mean glucose ± STD during ipGTTs for offspring of maternal diabetes, paternal diabetes and controls are shown for 14 (<b>panel e</b>) and 26 week (<b>panel f</b>) old males. Glucose clearance after ip bolus of glucose (ipGTT) was significantly impaired at all time points for offspring of <b>maternal</b> diabetes, and at 30 and 60 minutes in 14 week old mice, and at 60 minutes after injection in 26 week old offspring of <b>paternal</b> diabetes. * Denotes statistically significant difference vs. control (*p<0.05, ** p<0.01, *** p<0.001).</p>", "links"=>[], "tags"=>["outcomes", "wildtype"], "article_id"=>206357, "categories"=>["Chemistry", "Physiology", "Genetics"], "users"=>["Corinna Grasemann", "Maureen J. Devlin", "Paulina A. Rzeczkowska", "Ralf Herrmann", "Bernhard Horsthemke", "Berthold P. Hauffa", "Marc Grynpas", "Christina Alm", "Mary L. Bouxsein", "Mark R. Palmert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050210.g003", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Metabolic_Outcomes_in_Wildtype_Male_Offspring_/206357", "title"=>"Metabolic Outcomes in Wildtype Male Offspring.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-28 01:45:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/536062"], "description"=>"<p>Boxplots showing the smallest observation (lower bar), lower and upper quartile (box), median (line in box) and largest observation (upper bar) of male (left) and female (right) offspring of controls (open bars), paternal diabetes (longitudinal shading) and maternal diabetes (diagonal shading) for Percent of distal femur Bone Volume/Trabecular Volume (BV/TV %) at 14 and 26 weeks of age. * indicates p<0.05 vs. control.</p>", "links"=>[], "tags"=>["distal", "femur"], "article_id"=>206550, "categories"=>["Chemistry", "Physiology", "Genetics"], "users"=>["Corinna Grasemann", "Maureen J. Devlin", "Paulina A. Rzeczkowska", "Ralf Herrmann", "Bernhard Horsthemke", "Berthold P. Hauffa", "Marc Grynpas", "Christina Alm", "Mary L. Bouxsein", "Mark R. Palmert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050210.g004", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Percent_of_distal_femur_Bone_Volume_Trabecular_Volume_Tb_BV_TV_/206550", "title"=>"Percent of distal femur Bone Volume/Trabecular Volume (Tb.BV/TV (%)).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-28 01:49:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/535553"], "description"=>"<p>Generation of wildtype C57Bl6/J offspring of <b>a</b>) diabetic, heterozygous Akita females, <b>b</b>) diabetic, heterozygous Akita males and <b>c</b>) wildtype mice (control offspring). Offspring of Akita mothers will have been exposed to <i>in-utero</i> hyperglycemia. All offspring of Akita parents were genotyped and only the wildtype offspring were assessed subsequently.</p>", "links"=>[], "tags"=>["breeding"], "article_id"=>206043, "categories"=>["Chemistry", "Physiology", "Genetics"], "users"=>["Corinna Grasemann", "Maureen J. Devlin", "Paulina A. Rzeczkowska", "Ralf Herrmann", "Bernhard Horsthemke", "Berthold P. Hauffa", "Marc Grynpas", "Christina Alm", "Mary L. Bouxsein", "Mark R. Palmert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050210.g001", "stats"=>{"downloads"=>2, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_of_Breeding_Strategy_/206043", "title"=>"Schematic of Breeding Strategy.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-28 01:40:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/536228"], "description"=>"<p>Mean+STD and animal numbers (n) as well as numbers of pregnancies () are provided for male offspring at 14 and 26 weeks of age for phenotypic markers obtained in offspring of maternal diabetes, paternal diabetes and controls. Significant differences to control offspring (p<0.05) are highlighted in grey shaded boxes (*, p<0.05).</p><p>AUC: Area under the curve for glucose response after ipGTT, BMD: bone mineral density, BMC: bone mineral content, LBW: lean body weight, BFAT: body fat, Tb.Th.: trabecular thickness, Tb.N.: number of trabeculae, Cort. Area: Cortical area, BA/TA: Bone area/trabecular area, Cort. Th.: Cortical thickness.</p>", "links"=>[], "tags"=>["metabolic", "skeletal", "markers", "offspring", "separated"], "article_id"=>206717, "categories"=>["Chemistry", "Physiology", "Genetics"], "users"=>["Corinna Grasemann", "Maureen J. Devlin", "Paulina A. Rzeczkowska", "Ralf Herrmann", "Bernhard Horsthemke", "Berthold P. Hauffa", "Marc Grynpas", "Christina Alm", "Mary L. Bouxsein", "Mark R. Palmert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050210.t003", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phenotypic_results_for_metabolic_and_skeletal_markers_in_female_offspring_separated_by_age_and_group_/206717", "title"=>"Phenotypic results for metabolic and skeletal markers in female offspring separated by age and group.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-11-28 01:51:57"}

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Relative Metric

{"start_date"=>"2012-01-01T00:00:00Z", "end_date"=>"2012-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[322, 550, 671, 773, 864, 955, 1048, 1135, 1223, 1308, 1387, 1465, 1534, 1602, 1673, 1744, 1813, 1885, 1955, 2026, 2093, 2160, 2228, 2290, 2349]}, {"subject_area"=>"/Biology and life sciences/Anatomy", "average_usage"=>[308, 530, 649, 751, 844, 933, 1021, 1107, 1194, 1277, 1357, 1426, 1501, 1572, 1634, 1702, 1768, 1838, 1910, 1976, 2046, 2114, 2181, 2241, 2298]}, {"subject_area"=>"/Medicine and health sciences/Endocrinology", "average_usage"=>[315, 561, 698, 824, 914, 1014, 1127, 1230, 1339, 1437, 1505, 1602, 1669, 1731, 1794, 1868, 1945, 2023, 2083, 2140, 2231, 2286, 2342, 2407, 2460]}, {"subject_area"=>"/Medicine and health sciences/Metabolic disorders", "average_usage"=>[329, 565, 687, 799, 892, 997, 1113, 1208, 1308, 1395, 1473, 1546, 1623, 1690, 1762, 1828, 1893, 1960, 2030, 2087, 2146, 2207, 2272, 2319, 2370]}, {"subject_area"=>"/Physical sciences/Chemistry", "average_usage"=>[302, 508, 622, 720, 804, 888, 973, 1054, 1141, 1219, 1299, 1370, 1442, 1511, 1574, 1644, 1711, 1782, 1846, 1911, 1971, 2030, 2097, 2155, 2217]}]}
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