Direct effect of insulin and insulin-like growth factor-I on the secretory activity of rat pancreatic beta cells

Abstract

Purified pancreatic Beta cells were labelled with 3H-tyrosine before studying their secretory activity in perifusion. At 1.4 mmol/l glucose, the cells released similar fractions (0.01% per min) of their contents in preformed and in newly formed insulin. At 20 mmol/l glucose plus 10(-8) mol/l glucagon, these fractional release rates increased by 16 and 40-fold respectively. The preferential release of newly synthesized as compared to stored insulin is attributable to a heterogeneity in individual cell responses. The secretory responsiveness to glucose plus glucagon was completely suppressed by 10(-7) mol/l clonidine. Insulin induced a 20% reduction at 10(-6) mol/l, but remained without effect at 10(-7) mol/l. Insulin-like growth factor-I provoked a 30% decrease at 5.10(-9) mol/l. It is concluded that the type-I insulin-like growth factor receptors on pancreatic Beta cells mediate a suppressive action on the insulin release process. Their high affinity for insulin-like growth factor-I allows physiologic levels of this peptide to participate in the regulation of insulin release. Their low affinity for insulin provides the basis for a minor feedback action by this hormone at concentrations exceeding the normal circulating levels.

Effect of PAO (phenylarsine oxide) on the Inhibitory Effect of Insulin and IGF-1 on Insulin Release from INS-1 Cells

“…PAO reversed the inhibition of insulin release in the case of both insulin and IGF-1. This may strengthen the argument that insulin and IGF-1 act via the same receptor as was suggested [22,23].…”

“…The effect of insulin is most prominent at rather high concentrations being present in the intercellular space of pancreatic B-cells which is in favour of an interaction of insulin with IGF-1 receptors as was postulated by Schravendijk [22,23]. PAO reversed the inhibition of insulin release in the case of both insulin and IGF-1.…”

“…Since insulin effects are generally affected by PAO as was mentioned before, PAO effects on insulin-modulated insulin release were investigated using INS-1 cells, an insulin secreting cell line. Since there is an interaction between PAO and IGF-1 and since IGF-1 receptors may be involved in insulin negative feedback effects on insulin release [22,23], the interaction between IGF-1 and PAO was investigated as well.…”

Attenuation of insulin secretion by insulin-like growth factor 1 is mediated through activation of phosphodiesterase 3B

“…The anti-insulin monoclonal antibody was from Sigma. The anti-IGF-1 receptor and anti-insulin receptor antibodies were from Santa Cruz Biotechnology; both antibodies were raised against the N-terminal unique sequences (amino acids [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] of the corresponding receptor. IGF-1 was from Becton Dickinson or GIBCO͞BRL.…”

“…Insulin-like growth factor 1 (IGF-1) is one such example. When infused into normal healthy human subjects at a dose not causing hypoglycemia, IGF-1 can decrease the circulating insulin level (2) and IGF-1 can directly attenuate insulin secretion from isolated primary rat pancreatic ␤ cells (3). Insulin itself has been postulated to exert a negative-feedback control of its own secretion (4,5).…”