Journal article
Host Factors Alter Effects of Angiopoietin-Like Protein 8 on Glucose Homeostasis in Diabetic Mice
Journal of diabetes mellitus, Vol.6(4), pp.277-290
11/01/2016
DOI: 10.4236/jdm.2016.64029
PMCID: PMC6859639
PMID: 31741751
Abstract
Recovery of functional beta cell mass offers a biological cure for type 1 diabetes. However, beta cell mass is difficult to regain once lost since the proliferation rate of beta cells after youth is very low. Angiopoietin like-protein 8 (ANGPTL8), a peptide that has a role in the regulation of lipoprotein lipase activity, was reported to increase beta cell proliferation in mice in 2013. Subsequent studies of human ANGPTL8 for short term (3 to 8 days) in non-diabetic mice showed little or no increase in beta cell proliferation. Here, we examined the effect of ANGPTL8 on glucose homeostasis in models that have not been examined previously. We expressed mouse ANGPTL8 using adenovirus in 2 mouse models of diabetes (streptozotocin and Non-Obese Diabetic (NOD) mice) over 2 weeks. Also, we tested ANGPTL8 in NOD mice deficient in leukocyte 12-lipoxygenase (12LO), an enzyme that contributes to insulitis and loss of beta cell function in NOD, in an effort to determine whether 12LO deficiency alters the response to ANGPTL8. Adenovirus-mediated expression of ANGPTL8 lowered blood glucose levels in streptozotocin treated mice without an increase in beta cell proliferation or serum insulin concentration. While ANGPTL8 did not reverse hyperglycemia in overtly hyperglycemic NOD mice or alter glucose homeostasis of non-diabetic NOD mice, ANGPTL8 reduced blood glucose levels in 12LOKO NOD mice. However, the lower glucose levels in 12LOKO NOD were not associated with higher serum insulin levels or beta cell proliferation. In summary, while mouse ANGPTL8 does not increase beta cell proliferation in NOD mice or streptozotocin treated mice in agreement with studies in non-diabetic mice, it lowers blood glucose levels in multiple low-dose streptozotocin induced diabetes and 12LO deficiency indicating that host factors influence the impact of ANGPTL8 on glucose homeostasis.
Details
- Title: Subtitle
- Host Factors Alter Effects of Angiopoietin-Like Protein 8 on Glucose Homeostasis in Diabetic Mice
- Creators
- Sichen Liu - Eastern Virginia Medical SchoolEmily M. Smith - Eastern Virginia Medical School, Department of Internal Medicine, Strelitz Diabetes Center, Norfolk, VA, USA Department of Internal Medicine, Fraternal Order of Eagles Diabetes Research Center, The University of Iowa Carver College of Medicine, Iowa City, IA, USATimothy H. King - University of IowaLindsey Glenn - Eastern Virginia Medical SchoolMichelle Trevino - Eastern Virginia Medical SchoolSo Hyun Park - Eastern Virginia Medical School, Department of Internal Medicine, Strelitz Diabetes Center, Norfolk, VA, USA Department of Internal Medicine, Fraternal Order of Eagles Diabetes Research Center, The University of Iowa Carver College of Medicine, Iowa City, IA, USAYui Machida - Eastern Virginia Medical SchoolCiriaco Villaflor - Eastern Virginia Medical SchoolWojciech Grzesik - Eastern Virginia Medical SchoolMargaret A. Morris - Eastern Virginia Medical School, Department of Internal Medicine, Strelitz Diabetes Center, Norfolk, VA, USA Department of Internal Medicine, Fraternal Order of Eagles Diabetes Research Center, The University of Iowa Carver College of Medicine, Iowa City, IA, USAYumi Imai - Eastern Virginia Medical SchoolJerry L. Nadler - Eastern Virginia Medical School
- Resource Type
- Journal article
- Publication Details
- Journal of diabetes mellitus, Vol.6(4), pp.277-290
- DOI
- 10.4236/jdm.2016.64029
- PMID
- 31741751
- PMCID
- PMC6859639
- NLM abbreviation
- J Diabetes Mellitus
- ISSN
- 2160-5831
- eISSN
- 2160-5858
- Language
- English
- Date published
- 11/01/2016
- Academic Unit
- Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984362285302771
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