Gastric inhibitory polypeptide (GIP) is a gut derived peptide with multiple emerging physiological actions. Effects of pregnancy and lactation on GIP secretion and related gene expression were studied in Wistar rats. Pregnancy moderately increased feeding (p<0.05), whilst lactation substantially increased food intake (p<0.01 to p<0.001). Circulating GIP was unchanged during pregnancy, but non-fasting plasma glucose was significantly (p<0.01) decreased and insulin increased (p<0.05). Lactation was associated with elevated circulating GIP concentrations (p<0.001) without change of glucose or insulin. Oral glucose resulted in a significantly (p<0.001) decreased glycaemic excursion despite similar glucose-induced GIP and insulin concentrations in lactating rats. Pregnant rats had a similar glycaemic excursion but exhibited significantly lowered (p<0.05) GIP accompanied by elevated (p<0.001) insulin levels. Pregnant rats exhibited increased (p<0.001) islet numbers and individual islet areas were enlarged (p<0.05). There were no significant differences in islet alpha-cell areas, but all groups of rats displayed co-expression of glucagon and GIP in alpha-cells. Lactating rats exhibited significantly (p<0.01) increased intestinal weight, whereas intestinal GIP stores were significantly (p<0.01) elevated only in pregnant rats. Gene expression studies in lactating rats revealed prominent (p<0.01 to p<0.001) increases in mammary gland expression of genes involved in energy turnover, including GIP-R. GIP was present in intestines and plasma of 17 day old foetal rats, with substantially raised circulating concentrations in neonates throughout the period of lactation/suckling. These data indicate that changes in the secretion and action of GIP play an important role in metabolic adaptations during pregnancy and especially lactation.

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Effects of insulin excess and deficiency on glucose-dependent insulinotropic polypeptide (GIP) was examined in rats following insulinoma transplantation or streptozotocin (STZ) administration. Over 14 days, food intake was increased (p < 0.001) in both groups of rats, with decreased body weight (p < 0.01) in STZ rats. Non-fasting plasma glucose levels were decreased (p < 0.01) and plasma insulin levels increased (p < 0.001) in insulinoma-bearing rats, whereas STZ treatment elevated glucose (p < 0.001) and decreased insulin (p < 0.01). Circulating GIP concentrations were elevated (p < 0.01) in both animal models. At 14 days, oral glucose resulted in a decreased glycaemic excursion (p < 0.05) with concomitant elevations in insulin release (p < 0.001) in insulinoma-bearing rats, whereas STZ-treated rats displayed similar glucose-lowering effects but reduced insulin levels (p < 0.01). GIP concentrations were augmented in STZ rats (p < 0.05) following oral glucose. Plasma glucose and insulin concentrations were not affected by oral fat, but fat-induced GIP secretion was particularly (p < 0.05) increased in insulinoma-bearing rats. Exogenous GIP enhanced (p < 0.05) glucose-lowering in all groups of rats accompanied by insulin releasing (p < 0.001) effects in insulinoma-bearing and control rats. Both rat models exhibited increased (p < 0.001) intestinal weight but decreased intestinal GIP concentrations. These data suggest that circulating insulin has direct and indirect effects on the synthesis and secretion of GIP.