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Pancreatic islet blood flow in normal and obese-hyperglycemic (ob/ob) mice
P O Carlsson1, A Andersson, L Jansson
1Department of Medical Cell Biology, Uppsala University, Sweden.
Abstract:
The present study evaluated whether a microsphere technique could be used for islet blood flow measurements in anesthetized mice. When this was confirmed, we applied the technique in different strains of mice. Approximately 9 x 10(4) microspheres could be given without interfering with mean arterial blood pressure. Mixing of the microspheres with arterial blood was adequate, and the extraction of microspheres in capillary beds was nearly 100%. In NMRI mice whole pancreatic blood flow was estimated to be 0.54 +/- 0.11 ml.min-1.g pancreatic tissue-1 and islet blood flow to be 18 +/- 4 microliters.min-1.g pancreas-1 (n = 12 animals per experiment), whereas corresponding values in lean C57Bl/6 mice were twice as high. In C57Bl/6 mice glucose (3 g/kg iv) doubled islet blood flow without affecting whole pancreatic blood flow, whereas no effect was seen after an equimolar dose of 3-O-methylglucose. In obese-hyperglycemic C57Bl/6 mice, islet blood flow was more than five times higher than in the lean C57Bl/6 mice when expressed as blood flow per gram pancreas. However, when islet blood perfusion was corrected for islet weight, it was lower in the obese than in the lean mice, suggesting an impaired ability in obese mice to increase blood flow in concert with the increased islet mass. This may contribute to the insufficient insulin secretion and resulting hyperglycemia seen in these animals.
Insights
This study validates a microsphere method for measuring islet blood flow in mice. Obese mice show impaired islet blood flow regulation, potentially causing hyperglycemia.
Area of Science:
- Physiology
- Endocrinology
- Cardiovascular Research
Background:
- Accurate measurement of islet blood flow is crucial for understanding pancreatic function and metabolic diseases.
- Previous methods for assessing islet perfusion have limitations.
Purpose of the Study:
- To validate a microsphere technique for measuring islet blood flow in mice.
- To investigate pancreatic and islet blood flow in different mouse strains and under physiological challenge.
Main Methods:
- Utilized a microsphere technique for quantifying blood flow in anesthetized mice.
- Administered microspheres intravenously and measured arterial blood pressure.
- Calculated whole pancreatic and islet blood flow in NMRI, lean C57Bl/6, and obese-hyperglycemic C57Bl/6 mice.
- Assessed the effect of glucose and 3-O-methylglucose on blood flow.
Main Results:
- The microsphere technique proved reliable, with near 100% extraction and no interference with blood pressure.
- Islet blood flow was significantly higher in lean C57Bl/6 mice compared to NMRI mice.
- Glucose administration doubled islet blood flow in lean mice, but 3-O-methylglucose had no effect.
- Obese mice exhibited higher islet blood flow per gram of pancreas, but lower perfusion per islet mass compared to lean mice.
Conclusions:
- The microsphere technique is a valid method for determining islet blood flow in mice.
- Obese mice demonstrate an impaired capacity to regulate islet blood flow relative to islet mass, contributing to hyperglycemia.
- Findings suggest a link between altered islet perfusion and insufficient insulin secretion in obese hyperglycemia.