التفاصيل البيبلوغرافية
| العنوان: |
Radiomanganese PET Detects Changes in Functional β-Cell Mass in Mouse Models of Diabetes. |
| المؤلفون: |
Hernandez, Reinier, Graves, Stephen A., Gregg, Trillian, VanDeusen, Halena R., Fenske, Rachel J., Wienkes, Haley N., England, Christopher G., Valdovinos, Hector F., Jeffery, Justin J., Barnhart, Todd E., Severin, Gregory W., Nickles, Robert J., Kimple, Michelle E., Merrins, Matthew J., Weibo Cai, Cai, Weibo |
| المصدر: |
Diabetes; Aug2017, Vol. 66 Issue 8, p2163-2174, 12p |
| مصطلحات موضوعية: |
B cells, CELL physiology, TYPE 1 diabetes, TYPE 2 diabetes, INSULIN, POSITRON emission tomography, MAGNETIC resonance imaging, LABORATORY mice, ANIMAL experimentation, CALCIUM, COMPARATIVE studies, DIABETES, ISLANDS of Langerhans, MANGANESE, RESEARCH methodology, MEDICAL cooperation, MICE, PANCREAS, RADIOPHARMACEUTICALS, RESEARCH, RESEARCH funding, EVALUATION research, CASE-control method, DISEASE progression, CELL size, PHARMACODYNAMICS, PHYSIOLOGY |
| مستخلص: |
The noninvasive measurement of functional β-cell mass would be clinically valuable for monitoring the progression of type 1 and type 2 diabetes as well as the viability of transplanted insulin-producing cells. Although previous work using MRI has shown promise for functional β-cell mass determination through voltage-dependent Ca2+ channel (VDCC)-mediated internalization of Mn2+, the clinical utility of this technique is limited by the cytotoxic levels of the Mn2+ contrast agent. Here, we show that positron emission tomography (PET) is advantageous for determining functional β-cell mass using 52Mn2+ (t1/2: 5.6 days). We investigated the whole-body distribution of 52Mn2+ in healthy adult mice by dynamic and static PET imaging. Pancreatic VDCC uptake of 52Mn2+ was successfully manipulated pharmacologically in vitro and in vivo using glucose, nifedipine (VDCC blocker), the sulfonylureas tolbutamide and glibenclamide (KATP channel blockers), and diazoxide (KATP channel opener). In a mouse model of streptozotocin-induced type 1 diabetes, 52Mn2+ uptake in the pancreas was distinguished from healthy controls in parallel with classic histological quantification of β-cell mass from pancreatic sections. 52Mn2+-PET also reported the expected increase in functional β-cell mass in the ob/ob model of pretype 2 diabetes, a result corroborated by histological β-cell mass measurements and live-cell imaging of β-cell Ca2+ oscillations. These results indicate that 52Mn2+-PET is a sensitive new tool for the noninvasive assessment of functional β-cell mass. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
