| Summary: | Northern elephant seal pups fast for 2–3 months post‐weaning during which they show various symptoms associated with insulin resistance (e.g. reduced glucose clearance and insulin signaling, and increased plasma lipids). However, because fasting pups also show decreased plasma insulin, it remains unclear whether or not decreased insulin action is a result of decreased insulin sensitivity. To address the hypothesis that fasting induces insulin resistance in elephant seal pups, early (n=5) and late (n=5) fasted seals were infused with a mass specific dose of insulin (0.065 U/kg). Glucose clearance was similar in both periods (1.08 mg/dL/min vs. 1.05 mg/dL/min), however insulin‐signaling activity was 15% lower in late fasted seals. Plasma lipids were decreased to a greater degree in the early fasted seals than in late fasted seals. Glucose clearance of fasting pups is 70% slower than seen in insulin sensitive mammals. Additionally, reduced insulin signaling activity paired with reduced inhibition of lipolysis in late fasted seals demonstrates that insulin sensitivity declines further with fasting. These results definitively show that fasting elephant seal pups are insulin resistant. Furthermore, because fasting, insulin resistant pups are able to maintain control of their metabolism, these results strengthen the idea that insulin resistance is an adaptation to prolonged fasting.
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