Loss of beta-cell mass leads to a reduction of pulse mass with normal periodicity, regularity and entrainment of pulsatile insulin secretion in G�ttingen minipigs

Abstract

Aims/hypothesis. Type 2 diabetes is associated with impaired insulin action and secretion, including disturbed pulsatile release. Impaired pulsatility has been related to impaired insulin action, thus providing a possible link between release and action of insulin. Furthermore, progressive loss of beta-cell mass has been implicated in the pathogenesis of Type 2 diabetes. The aim of this study was to evaluate a possible link between loss of beta-cell mass and impaired pulsatile insulin secretion with special focus on glucose responsiveness of insulin secretion. Methods. The kinetic and dynamic profiles of insulin in Göttingen minipigs are favourable for studies on pulsatility and a model of diabetes with reduced betacell mass has recently been established. Pigs were studied before (n=14) and after (n=10) reduction of beta-cell mass by nicotinamide (67 mg/kg) and streptozotocin (125 mg/kg) from 17.7±4.7 (normal animals, n=5) to 6.1±2.0 mg/kg. Pulsatile insulin secretion was examined during basal (n=8 normal, n=6 beta-cell reduced) and glucose entrained (n=6 normal, n=4 betacell reduced) conditions. Insulin concentration time series were analysed by autocorrelation and spectral analyses for periodicities and regularity, and by deconvolution for pulse frequency, mass and amplitude. Results. Reduction of beta-cell mass and secondary hyperglycaemia resulted in correspondingly (r=0.7421, p=0.0275) reduced pulse mass (42% of normal during basal and 31% during entrained conditions) with normal periodicity (6.6±2.2 vs 5.8±2.4 min, p=0.50), regularity and entrainability of insulin secretion. Conclusion/interpretation. Neither beta-cell loss, nor 2 weeks of slight hyperglycaemia, as seen in the betacell-reduced minipig, probably accounts for the disturbed insulin pulsatility observed in human Type 2 diabetes. [Diabetologia (2003) 46:195-202]

An F2 Pig Resource Population as a Model for Genetic Studies of Obesity and Obesity-Related Diseases in Humans: Design and Genetic Parameters

“…In humans normal fasting plasma glucose levels are below 5.6 mmol/L, impaired plasma glucose levels are between 5.6 and 7 mmol/L, while type 2 diabetes has plasma glucose levels above 7 mmol/L. Previous research indicated lower fasting plasma glucose levels for the minipig (i.e., 3.6 mmol/L Larsen et al, 2003), whereas the domestic pig is estimated at the same level as humans (Larsen and Rolin, 2004). In our resource population, FGLs range between 1.80 and 11.15, with an average of 4.50 (SE = 2.18).…”

Μελέτη της κατά ώσεις έκκρισης της ινσουλίνης και της αντίστασης στην ινσουλίνη σε ασθενείς με σακχαρώδη διαβήτη τύπου 2 και νοσογόνο παχυσαρκία πριν και μετά την χολοπαγκρεατική εκτροπή με γαστρική παράκαμψη Roux-en-Y

“…Η ελάττωση του αριθμού των β-κυττάρων στο ΣΔ δε φαίνεται να την εξηγεί. Έχει δειχθεί ότι η καταστροφή των β-κυττάρων οδηγεί σε ελάττωση του εύρους των ώσεων, χωρίς επίδραση στη συχνότητα [207] [208], ούτε στο συντονισμό με τη γλυκόζη [209]. Πιθανότατα οφείλεται σε μία διαταραχή οποιουδήποτε από τα πολυάριθμα μοριακά βήματα που μεσολαβούν μεταξύ της πρόσληψης και της μεταφοράς της γλυκόζης στο β-κύτταρο και της εξωκύτωσης των κοκκίων της ινσουλίνης (σύζευξη ερεθίσματοςέκκρισης-stimulus-secretion coupling).…”