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Insulin during infancy attenuates insulin-induced hypoglycemia in adult male rats
C I Thompson1, J W Munford, R M Ryker
1Department of Psychology, Wabash College, Crawfordsville, IN 47933, USA. ThompsoC@Wabash.edu
Insights
Infant insulin exposure in male rats attenuated adult hypoglycemia when food was withheld. Early insulin or 2-deoxy-D-glucose (2DG) treatments altered glucose regulation in male rats, but not females.
Area of Science:
- Endocrinology
- Developmental Biology
- Metabolic Regulation
Background:
- Insulin and glucose regulation are critical during development.
- Early life exposures can have long-term metabolic consequences.
- The impact of infant insulin exposure on adult glucose homeostasis is not fully understood.
Purpose of the Study:
- To investigate the long-term effects of infant insulin or 2-deoxy-D-glucose (2DG) administration on glucose regulation in rats.
- To determine if early metabolic challenges influence adult glycemic control, particularly in response to insulin.
Main Methods:
- Rat pups received daily injections of insulin, 2DG, or saline from postnatal Days 9-20.
- Plasma glucose levels were measured at various time points, including baseline, after insulin challenge, and under fed/fasted conditions.
- Body weight, plasma insulin, liver, and kidney weights were assessed in adulthood.
Main Results:
- Baseline plasma glucose was lower in rats treated with insulin or 2DG during infancy compared to controls.
- Adult male rats exposed to insulin during infancy showed attenuated hypoglycemia when challenged with insulin and food was withheld.
- Females and fed conditions did not show significant effects of early treatment on glucose regulation.
Conclusions:
- Preweaning insulin exposure can alter glucose regulation in adult male rats, specifically attenuating hypoglycemia under fasted conditions.
- Early metabolic programming through insulin or 2DG can lead to lasting changes in glucose homeostasis.
- Sex-specific effects of early metabolic interventions on glucose regulation warrant further investigation.
Abstract:
To examine whether insulin during infancy affects later glucose regulation, 60 rat pups of both sexes were injected daily on postnatal Days 9-20 with either insulin (2 or 8 U/kg), 2-deoxy-D-glucose (2DG; 200 or 400 mg/kg), or saline. Two hours postinjection on Day 15, pups given insulin were hypoglycemic and pups given 2DG were hyperglycemic; both groups were normoglycemic at 6 h. The two insulin doses produced similar long-term effects, as did the 2DG doses, so doses were combined to make single insulin and 2DG groups. On Day 44, baseline plasma glucose for rats given insulin or 2DG during infancy was below saline control levels (111.3, 114.5, and 120.7 mg/dL, respectively, p < 0.05). On Days 60 and 62, plasma glucose was assessed 2 h after injection of 3 U/kg insulin; food was allowed between the insulin injection and the glucose test on only one of these days. When food was present after injection of insulin, the early treatments did not influence either amount of food ingested or plasma glucose levels. When food was withheld, however, males given insulin before weaning maintained a higher plasma glucose than did males given 2DG or saline before weaning (67.4, 40.1, and 16.4 mg/dL, respectively, p < 0.01); females were unaffected by the early treatment. Postweaning body weights did not differ from control values for rats given early insulin or 2DG. On Day 72, there were no effects of early treatment on plasma insulin, plasma glucose, liver weight, or kidney weight. These results suggest that preweaning exposure to insulin attenuates the hypoglycemia of adult males given insulin without food.