Pharmacological Agents That Directly Modulate Insulin Secretion

2003 ◽  
Vol 55 (1) ◽  
pp. 105-131 ◽  
Author(s):  
Máire E. Doyle ◽  
Josephine M. Egan
Keyword(s):  
Insulin Secretion ◽  
Pharmacological Agents

Mild streptozotocin diabetes in the Göttingen minipig. A novel model of moderate insulin deficiency and diabetes

2002 ◽  
Vol 282 (6) ◽  
pp. E1342-E1351 ◽  
Author(s):  
Marianne O. Larsen ◽  
Michael Wilken ◽  
Carsten F. Gotfredsen ◽  
Richard D. Carr ◽  
Ove Svendsen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Regression Line ◽  
Cell Mass ◽  
Area Under The Curve ◽  
Streptozotocin Diabetes ◽  
Steep Slope ◽  
Insulin Deficiency ◽  
Β Cell ◽  
Pharmacological Agents ◽  
Novel Model

Nonrodent models of diabetes are needed for practical and physiological reasons. Induction of mild insulin-deficient diabetes was investigated in male Göttingen minipigs by use of streptozotocin (STZ) alone (75, 100, and 125 mg/kg) or 125 mg/kg combined with pretreatment with nicotinamide (NIA; 0, 20, 67, 100, 150, and 230 mg/kg). Use of NIA resulted in a less steep slope of the regression line between fasting plasma glucose and changing doses compared with STZ [−7.0 ± 1.4 vs. 29.7 ± 7.0 mM · mg−1· kg−1, P < 0.0001]. Intermediate NIA doses induced moderate changes of glucose tolerance [glucose area under the curve increased from 940 ± 175 to 1,598 ± 462 mM · min, P < 0.001 (100 mg/kg) and from 890 ± 109 to 1,669 ± 691 mM · min, P = 0.003 (67 mg/kg)] with reduced insulin secretion [1,248 ± 602 pM · min after 16 days and 1,566 ± 190 pM · min after 60 days vs. 3,251 ± 804 pM · min in normal animals ( P < 0.001)] and β-cell mass [5.5 ± 1.4 mg/kg after 27 days and 7.9 ± 4.1 mg/kg after 60 days vs. 17.7 ± 4.7 mg/kg in normal animals ( P = 0.009)]. The combination of NIA and STZ provided a model characterized by fasting and especially postprandial hyperglycemia and reduced, but maintained, insulin secretion and β-cell mass. This model holds promise as an important tool for studying the pathophysiology of diabetes and development of new pharmacological agents for treatment of the disease.

Insulin granule trafficking in β-cells: mathematical model of glucose-induced insulin secretion

2007 ◽  
Vol 293 (1) ◽  
pp. E396-E409 ◽  
Author(s):  
Alessandro Bertuzzi ◽  
Serenella Salinari ◽  
Geltrude Mingrone
Keyword(s):  
Experimental Data ◽  
Mathematical Model ◽  
Insulin Secretion ◽  
Cell Function ◽  
Model Parameters ◽  
Β Cells ◽  
Experimental Conditions ◽  
Pharmacological Agents ◽  
Hyperglycemic Clamp ◽  
Β Cell Function

A mathematical model that represents the dynamics of intracellular insulin granules in β-cells is proposed. Granule translocation and exocytosis are controlled by signals assumed to be essentially related to ATP-to-ADP ratio and cytosolic Ca2+ concentration. The model provides an interpretation of the roles of the triggering and amplifying pathways of glucose-stimulated insulin secretion. Values of most of the model parameters were inferred from available experimental data. The numerical simulations represent a variety of experimental conditions, such as the stimulation by high K+ and by different time courses of extracellular glucose, and the predicted responses agree with published experimental data. Model capacity to represent data measured in a hyperglycemic clamp was also tested. Model parameter changes that may reflect alterations of β-cell function present in type 2 diabetes are investigated, and the action of pharmacological agents that bind to sulfonylurea receptors is simulated.

Intraisiet somatostatin inhibits insulin secretion via SSTR5 in the isolated perfused mouse pancreas model

2001 ◽  
Vol 120 (5) ◽  
pp. A133-A133
Author(s):  
T TIRONE ◽  
S MOLDOVAN ◽  
M NORMAL ◽  
F DEMAYO ◽  
F CHARLESBRUNICARDI
Keyword(s):  
Insulin Secretion ◽  
Mouse Pancreas
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