Endocrine and Metabolic Insights from Pancreatic Surgery

Abstract

Although it is well established that diabetes can also develop as a result of diseases or maneuvers on the exocrine pancreas, the complex relationship between glucose disorders and underlying pancreatic disease is still debated. There is evidence that several features linked to pancreatic diseases can modify endocrine and metabolic conditions before and after surgery. However, pancreatic surgery provides a rare opportunity to correlate in vivo endocrine and metabolic pathways with ex vivo pancreatic samples, to examine the endocrine and metabolic effects of acute islet removal, and finally to clarify the pathogenesis of diabetes. This approach could therefore represent a unique method to shed light on the molecular mechanisms, predicting factors, and metabolic consequences of insulin resistance, islet plasticity, β cell failure, and type 2 diabetes.

Pancreaticoduodenectomy model demonstrates a fundamental role of dysfunctional β cells in predicting diabetes

“…Several studies have examined the metabolic changes occurring following partial pancreatectomy in humans (14,15) and have suggested that the acute removal of beta-cell mass inevitably accelerates a decline in betacell functional capacity, already "stressed" by the attempt to compensate for increasing insulin demand. (7,16) In the present study we aim to evaluate: (1) the changes in beta-cell secretory capacity, modelled from an oral glucose tolerance test (OGTT) and hyperglycemic clamp (HC) in non-diabetic individuals before and after acute beta-cell reduction and (2) whether pre-existing insulin secretory defects can predict glucose disarrangements following a reduction in beta-cell mass.…”

Noradrenergic fibers are associated with beta-cell dedifferentiation and impaired beta-cell function in humans

“…Human islets have been previously described as sparsely innervated and the potential role of noradrenergic fibers in diabetes onset has been ascribed to the regulation of blood flow within the islet [17].Using electron microscopy we were instead able to observe that these fibers were in direct contact with endocrine cells bearing typical insulin granules and morphology [40,41], thus bona fide beta-cells, suggesting a direct interplay between innervation and beta-cells. Using the extraordinary advantage of the pancreatic surgery group and in vivo insulin secretion study [42], we linked innervation to beta-cell function and glucose tolerance. We verified whether noradrenergic fibers were related to altered insulin secretion.…”

A Systematic Comparison of Protocols for Recovery of High-Quality RNA from Human Islets Extracted by Laser Capture Microdissection

“…All experiments were performed on freshly isolated pancreas samples from living patients undergoing partial pancreatectomy. These are extremely valuable tissues, and we believe that pancreatic surgery provides a rare opportunity to correlate in vivo endocrine and metabolic pathways (before surgery) with ex vivo data generated after collecting the pancreatic samples [ 16 ]…”

“…All experiments were performed on freshly isolated pancreas samples from living patients undergoing partial pancreatectomy. These are extremely valuable tissues, and we believe that pancreatic surgery provides a rare opportunity to correlate in vivo endocrine and metabolic pathways (before surgery) with ex vivo data generated after collecting the pancreatic samples [16] Previous reports on cell culture and peripheral blood mononuclear cells (PBMCs) have reported that silica gel column technology using the RNeasy Mini-/Microkit is superior in its ability to extract high-quality RNA compared to protocols using the traditional guanidine isothiocyanate extraction method [17], which is mostly explained by the high binding power of silica gel columns. There also appears to be a different outcome in terms of RNA quantity and quality between the two methods.…”

“…We performed this process on islets extracted from 7 non-diabetic PP samples and 2 diabetic PP samples. To improve both the quantity and the quality of the RNA, we first performed RNA extraction on LCM-collected islets from one non-diabetic and one diabetic subject using Qiazol reagent as lysis cell buffer, which has been reported to produce high-quality RNA from rat pancreas [16]. We used samples that showed a better RIN after bioanalyzer evaluation following the purification step with the RNeasy Mini Clean-up kit (Qiagen Germantown, MD, USA).…”