Compensatory growth of pancreatic beta-cells in adult rats after short-term glucose infusion.
The extent to which adult pancreatic beta-cells can respond in vivo to a sustained glucose stimulus by increasing their mass through either hyperplasia or hypertrophy has remained unanswered. Therefore, we studied the in vivo effect of short-term (96-h) hyperglycemia on the growth of beta-cells by infusing adult rats with 35 or 50% glucose or 0.45% saline. After 96 h of glucose infusion, the beta-cell mass, quantified by point-counting morphometrics of immunoperoxidase-stained paraffin sections, showed a 50% increase (9.57 +/- 0.87 mg, n = 5, 50% glucose infused; 9.50 +/- 1.23, n = 7, 35% glucose infused; 6.15 +/- 0.55, n = 6, 0.45% saline infused). This growth was selective for beta-cells; the non-beta-cell mass was unchanged. The mitotic index, measured by accumulated mitotic frequency after a 4-h colchicine treatment, increased fivefold in glucose-infused animals compared to saline-infused animals. This enhanced replication of beta-cells provides evidence for increase in cell number or hyperplasia. In addition, hypertrophy of the beta-cell was also quantified. Mean cell volume, determined from the mean cell cross-sectional area measured planimetrically from low-magnification electron micrographs, increased to 150% of control values after 96 h of 50% glucose infusion. Seven days after the 96-h infusion, in reversal experiments, the beta-cell mass had not returned to saline-infused levels. In addition, the non-beta-cell mass of glucose-infused animals had increased. The mitotic index of the beta-cell of glucose-infused rats was, however, significantly lower than that of the saline controls, but the mean cell volume of the beta-cells remained elevated.(ABSTRACT TRUNCATED AT 250 WORDS)
Bonner-Weir
S
S
Elliot P. Joslin Research Laboratories, New England Deaconess Hospital, Boston, Massachusetts 02215.
Deery
D
D
Leahy
J L
JL
Weir
G C
GC
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005947:Glucose / Q000494:pharmacology*; D006965:Hyperplasia; D006984:Hypertrophy; D007263:Infusions, Parenteral; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000502:physiology*; D008297:Male; D008938:Mitosis; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose