Imaging β-Cell Function Using a Zinc-Responsive MRI Contrast Agent May Identify First Responder Islets

Abstract

An imaging method for detecting β-cell function in real-time in the rodent pancreas could provide new insights into the biological mechanisms involving loss of β-cell function during development of type 2 diabetes and for testing of new drugs designed to modulate insulin secretion. In this study, we used a zinc-responsive MRI contrast agent and an optimized 2D MRI method to show that glucose stimulated insulin and zinc secretion can be detected as functionally active “hot spots” in the tail of the rat pancreas. A comparison of functional images with histological markers show that insulin and zinc secretion does not occur uniformly among all pancreatic islets but rather that some islets respond rapidly to an increase in glucose while others remain silent. Zinc and insulin secretion was shown to be altered in streptozotocin and exenatide treated rats thereby verifying that this simple MRI technique is responsive to changes in β-cell function.

Radiological Modalities and Diabetes: A Review

“…Recently two vital approach has been employed for monitoring of B-cell function using MRI manganese -enhanced and zinc -responsive contrast agents. In addition, the proved of evidence that MRI are useful in the diagnosing and monitoring of immune cell infiltration of pancreas in DM patients [42]. It is reported in several studies that PET, MRI and US are employed in trails to evaluating the efficacy of different imaging modalities for visualizing transplanted islets.…”

Impact of dietary zinc on stimulated zinc secretion MRI in the healthy and malignant mouse prostate

“…It is thought that Zn 2+ aids in crystallization of insulin so that more can be packaged into small-sized granules which can easily migrate to the cell surface for exocytosis (8). Upon secretion of insulin in response to an increase in plasma glucose, the weakly bound Zn 2+ ions are also released and the excess Zn 2+ surrounding b-cells can be detected using optical dyes (9)(10)(11) or, as demonstrated recently, by use of a Zn-responsive MRI contrast agent in vivo (12)(13)(14)(15). Imaging glucose-stimulated zinc secretion (GSZS) from the in vivo pancreas by MRI not only detects individual islets in the intact pancreas but also distinguishes between islets that respond immediately to an increase in glucose (rapidly responding islets) from those that release insulin more slowly (14).…”

Mn(ii) complex impregnated porous silica nanoparticles as Zn(ii)-responsive “Smart” MRI contrast agent for pancreas imaging

“…Consequently, the concentration of Zn(II) ions across the extracellular space increases from 40 mM to 500 mM. 32 Hence, Zn(II) ion concentration-dependent contrast enhancement as a whole or as ''hot spots'' would reveal the pathological condition of the pancreas and/or the b-cells. [33][34][35] The association of the co-released free Zn(II) ions within a contrast agent in the presence of human serum albumin (HSA) protein has thus been considered when developing Zn(II)responsive contrast agents for the pancreas by engendering a slowly rotating ternary system.…”

“…Consequently, the concentration of Zn( ii ) ions across the extracellular space increases from 40 μM to 500 μM. 32 Hence, Zn( ii ) ion concentration-dependent contrast enhancement as a whole or as “hot spots” would reveal the pathological condition of the pancreas and/or the β-cells. 33–35…”