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Toxin-induced IDDM (insulin dependent diabetes mellitus) in the musk shrew
1Department of Parasitology, Hamamatsu University School of Medicine, Japan. ohno@hama-med.ac.jp
Abstract:
We administered streptozotocin (STZ) and alloxan (AL) to the musk shrew (Suncus murinus, Insectivora) to determine the effective diabetogenic dose of the two toxins for this species. A single intraperitoneal (i.p.) injection of 75 mg/kgBW or the consecutive 5-day s injection of 25 mg/kgBW of STZ to non-fasted shrews, effectively (100%) induced hyperglycemia (> or = 300 mg/dl) with hypoinsulinaemia (< 30% of control level) in male shrews at 10 days after administration. Morphological studies showed cytological changes of B cells in the pancreatic islets of diabetic shrews. Hyperglycemic shrews induced by STZ were thus in IDDM (insulin dependent diabetes mellitus), and showed high susceptibility to the diabetogenic effect of STZ as compared with rodents. Shrews showed a sex difference in the diabetogenic susceptibility to STZ as do mice (male > female). They also showed a species specific resistance to the diabetogenic effect of AL. Of the eight shrews (with 8-hr fasting) that has been treated with a single injection of 200 mg/kgBW of AL, seven (88%) survived at least 10 days, showing no signs of hyperglycemia. All shrews died within 3 day s after injection of 250 or 300 mg/kgBW. These results indicated that the STZ-induced diabetic shrew is a unique animal model and may be useful for IDDM research. On the other hand, the musk shrew was highly resistant to the diabetogenic effects of AL.
Insights
The musk shrew is highly susceptible to streptozotocin (STZ)-induced diabetes, making it a unique model for insulin-dependent diabetes mellitus (IDDM) research. However, it exhibits resistance to alloxan (AL).
Area of Science:
- Endocrinology
- Toxicology
- Animal Models
Background:
- Streptozotocin (STZ) and alloxan (AL) are diabetogenic agents used to induce diabetes in research animals.
- The musk shrew (Suncus murinus) is an understudied species in metabolic research.
Purpose of the Study:
- To determine the effective diabetogenic doses of STZ and AL in the musk shrew.
- To evaluate the musk shrew as a potential animal model for insulin-dependent diabetes mellitus (IDDM).
Main Methods:
- Musk shrews were administered varying doses of STZ and AL via intraperitoneal injection.
- Blood glucose and insulin levels were monitored.
- Pancreatic islet morphology was examined.
Main Results:
- STZ effectively induced hyperglycemia and hypoinsulinemia in male shrews at specific doses, consistent with IDDM.
- STZ-induced diabetic shrews exhibited cytological changes in pancreatic B cells.
- Musk shrews showed high susceptibility to STZ but significant resistance to AL, with high mortality at higher AL doses.
Conclusions:
- The STZ-induced diabetic musk shrew represents a unique and potentially valuable animal model for IDDM research.
- The musk shrew's resistance to AL differentiates it from rodent models.