Effect of Insulin on Acetylcholine‐Evoked Amylase Release and Calcium Mobilization in Streptozotocin‐Induced Diabetic Rat Pancreatic Acinar Cells

Abstract

This article investigated the effect of acetylcholine (ACh) on amylase secretion and cellular calcium homeostasis [Ca2+]i in streptozotocin (STZ; 60 mg kg(-1), intraperitoneally)-induced diabetic rats compared to age-matched controls in an attempt to understand the cellular mechanism of exocrine pancreatic insufficiency. ACh-evoked marked dose-dependent increases in amylase release from isolated pancreatic acini and acinar cells in healthy control rats. In diabetic acini and acinar cells, the ACh-evoked amylase release was significantly (P < 0.05) reduced compared to healthy acini and acinar cells. Insulin (10(-6)M) stimulated amylase release in both control and diabetic acini and acinar cells but with a much reduced effect in diabetic tissues. Combining insulin with ACh had no significant effect on amylase release compared to the effect of ACh alone. In fura-2 loaded pancreatic acinar cells of normal rats, ACh (10(-5)M) evoked a large initial rise (peak) in [Ca2+]i followed by a decline into a plateau phase. This effect of ACh was significantly (P < 0.05) reduced in fura-2 loaded diabetic acinar cells. In control cells, insulin had no significant effect on either basal or ACh evoked [Ca2+]i compared to the effect of ACh alone. In contrast, in diabetic acinar cells, insulin significantly (P < 0.05) attenuated the effect of ACh. In a normally free extracellular Ca2+ medium [Ca2+]o containing 1 mM EGTA, the ACh-evoked [Ca2+]i in normal healthy fura-2 loaded acini was similar to the response obtained with ACh in fura-2 loaded diabetic acini. Together, the results indicated that exocrine pancreatic insufficiency is associated with decreased [Ca2+]i due to less Ca2+ released from internal stores and less Ca2+ entering the cell from the extracellular medium.

The PKCβ/HuR/VEGF pathway in diabetic retinopathy

“…After ten days from STZ administration, blood glucose values in diabetic rats were significantly higher than the corresponding values in non-diabetic animals (408 ± 23 and 99 ± 14 mg/dl respectively; see Table 1). A decrease in body weight of diabetic rats was observed, as also reported by others [30].…”

Effect of <i>Catha edulis</i> (khat) on pancreatic functions in streptozotocin-induced diabetes in male Sprague-Dawley rats

“…On the other hand, the very low level of serum insulin in the diabetic control rats and rats treated with the high and low doses of khat emphasized that the rats were insulin deficient due to the destruction of pancreatic β-cells by the administration of STZ [ 18 , 24 ], while insulin-treated rats showed a significantly higher insulin level, which was due to daily injection of those rats with exogenous insulin (NovoMix 30 FlexPen). On the other hand, the significant increase in amylase with the slight increase in insulin in the high dose khat-treated rats could be due to the interrelation between the secretion of insulin and amylase [ 35 ]; such findings could also indicate that high dose khat-treated rats were able to preserve some β-cells, which might have been because the high dose of khat provides some antioxidant activity because of its higher content of phenolic compounds [ 7 , 12 , 20 , 41 ]. On the other hand, the low-density lipoprotein levels of the rats treated with the high and low doses of khat were significantly lower than that of the diabetic control, which could indicate that the considerable antioxidant activity of khat [ 41 ] could have ameliorated lipid peroxidation [ 37 ].…”

Serum Amylase Levels in Relation to Islet β Cell Function in Patients with Early Type 2 Diabetes

“…The basal mechanisms by which insulin regulates amylase production by pancreatic acinar cells had been addressed in previous studies [28–30]. Insulin acts by binding to its own receptor on acinar cells, leading to the stimulation and potentiation of amylase secretion through multiple signaling pathways, including regulation of amylase gene transcription and stimulation of the synthesis of the corresponding protein in acinar cells [31].…”

“…Insulin acts by binding to its own receptor on acinar cells, leading to the stimulation and potentiation of amylase secretion through multiple signaling pathways, including regulation of amylase gene transcription and stimulation of the synthesis of the corresponding protein in acinar cells [31]. Patel et al [30] showed that insulin could stimulate amylase release from acinar cells in healthy and diabetic rats, but with a much-reduced effect in diabetic rats. Moreover, studies in patients with diabetes mellitus showed pancreatic exocrine tissue fibrosis and a reduced response to hormonal stimulation [31,32].…”