Role of increased insulin demand in the adaptation of the endocrine pancreas to pregnancy

Abstract

During gestation the demand for insulin increases due to a decrease in insulin sensitivity of the maternal tissues. Simultaneously, pancreatic islet-cell proliferation, as well as insulin production and secretion increase. Both phenomena appear to be caused by the actions of pregnancy hormones. We studied the relationship between the two phenomena by investigating whether the supply of exogenous insulin affects the secretion of pregnancy hormones and islet function during gestation. For that purpose rats were treated with high doses of insulin (4.8 IU day-1 by sub-cutaneous osmotic mini pumps) so that the endogenous demand for insulin was fully satisfied from day 8-14 of gestation. Euglycaemia (5.0 mM) was maintained by intra venous infusion of glucose. The treatment suppressed insulin synthesis, as measured by in situ hybridization, in both pregnant and cyclic rats. In addition, in pregnant rats the increments in insulin secretion and in islet-cell proliferation were partly prevented. Furthermore, the data also suggest that in pregnant rats the treatment partly prevented the decrease in insulin sensitivity. Finally, the treatment did not affect the plasma concentrations of progesterone, prolactin and placental lactogen, but prevented the rise in growth hormone concentrations in pregnant rats. The present data suggest that, next to direct effects of pregnancy hormones and growth hormone on the pancreatic islets, a decreased insulin sensitivity in the maternal tissues, induced by actions of the same hormones, is involved in the regulation of islet function during gestation.

Glucose Homeostasis in Pre-diabetic NOD and Lymphocyte-Deficient NOD/SCID Mice During Gestation

“…Pregnancy is known to modulate glucose homeostasis and to induce gestational diabetes, possibly followed by permanent maternal diabetes [19][20][21][22]. Also, pregnancy in diabetic mothers may be associated with intrauterine death, perinatal mortality, and birth weight anomalies [23,24].…”

Waist circumference is the key risk factor for diabetes in Korean women with history of gestational diabetes

“…It has been suggested that gestational hormones are involved in metabolic changes of pregnancy, as hormones of the placental lactogen, growth hormone, and prolactin family enhances insulin production and release, as well as cell proliferation in islets of Langerhans. Simultaneously with the changes in the endocrine and the pancreas, the sensitivity of the maternal tissues for insulin decreases during pregnancy, thereby increasing the demand for insulin [19,20].…”

Progesterone stimulates pancreatic cell proliferation in vivo

“…This resulted in ten experimental groups: control intact female rats (n=7), progesterone-treated intact female rats (n=7), control OVX rats (n=5), progesterone-treated OVX rats (n=5), control OVX rats treated with E2 (n=5), progesteronetreated OVX rats treated with E2 (n=7), control intact male rats (n=5), progesterone-treated intact male rats (n=5), control TX rats (n=5) and progesterone-treated TX rats (n=6). After 6 days of continuous progesterone treatment IVGTTs were carried out as described previously (10). In short: at 1100 h the rats received a glucose injection (0.5 g/kg body weight, dissolved in saline) via the cannula in the right atrium.…”