Metabolic Regulation In Progression To Autoimmune Diabetes

Paper Info

Title
Metabolic Regulation In Progression To Autoimmune Diabetes

Abstract
Recent evidence from serum metabolomics indicates that specific metabolic disturbances precede beta-cell autoimmunity in humans and can be used to identify those children who subsequently progress to type 1 diabetes. The mechanisms behind these disturbances are unknown. Here we show the specificity of the pre-autoimmune metabolic changes, as indicated by their conservation in a murine model of type 1 diabetes. We performed a study in non-obese prediabetic (NOD) mice which recapitulated the design of the human study and derived the metabolic states from longitudinal lipidomics data. We show that female NOD mice who later progress to autoimmune diabetes exhibit the same lipidomic pattern as prediabetic children. These metabolic changes are accompanied by enhanced glucose-stimulated insulin secretion, normoglycemia, upregulation of insulinotropic amino acids in islets, elevated plasma leptin and adiponectin, and diminished gut microbial diversity of the Clostridium leptum group. Together, the findings indicate that autoimmune diabetes is preceded by a state of increased metabolic demands on the islets resulting in elevated insulin secretion and suggest alternative metabolic related pathways as therapeutic targets to prevent diabetes.

Year	DOI	Venue
2011	10.1371/journal.pcbi.1002257	PLOS COMPUTATIONAL BIOLOGY
Keywords	Field	DocType
amino acid,computational biology,cluster analysis,metabolome,insulin,risk factors	Downregulation and upregulation,Diabetes mellitus,NOD mice,Biology,Internal medicine,Adiponectin,Insulin,Insulin resistance,Type 1 diabetes,Autoimmunity,Endocrinology	Journal
Volume	Issue	ISSN
7	10	1553-734X
Citations	PageRank	References
2	0.39	8
Authors
20

Authors (20 rows)

Cited by (2 rows)

References (8 rows)

Name	Order	Citations	PageRank
Marko Sysi-Aho	1	28	1.93
Andrey Ermolov	2	2	0.39
Peddinti V. Gopalacharyulu	3	21	2.17
Abhishek Tripathi	4	60	6.35
Tuulikki Seppänen-Laakso	5	18	1.39
Johanna Maukonen	6	2	0.39
Ismo Mattila	7	2	0.39
Suvi T Ruohonen	8	2	0.39
Laura Vähätalo	9	2	0.39
Laxman Yetukuri	10	55	3.21
Taina Härkönen	11	2	0.39
Erno Lindfors	12	19	2.46
Janne Nikkilä	13	200	16.65
Jorma Ilonen	14	2	0.39
Olli Simell	15	2	0.73
Maria Saarela	16	2	0.39
Mikael Knip	17	2	0.39
Samuel Kaski	18	2755	245.52
Eriika Savontaus	19	2	0.39
Matej Oresic	20	323	34.23