Pancreatic islets are richly vascularized, and islet blood vessels are uniquely adapted to maintain and support the internal milieu of the islets favoring normal endocrine function. Islet blood flow is normally very high compared with that to the exocrine pancreas and is autonomously regulated through complex interactions between the nervous system, metabolites from insulin secreting β-cells, endothelium-derived mediators, and hormones. The islet blood flow is normally coupled to the needs for insulin release and is usually disturbed during glucose intolerance and overt diabetes. The present review provides a brief background on islet vascular function and especially focuses on available techniques to measure islet blood perfusion. The gold standard for islet blood flow measurements in experimental animals is the microsphere technique, and its advantages and disadvantages will be discussed. In humans there are still no methods to measure islet blood flow selectively, but new developments in radiological techniques hold great hopes for the future.
Pancreatic islet endothelial cells have in recent years been shown to support beta-cell mass and function by paracrine interactions. Recently, we identified an islets endothelial-specific glycoprotein, thrombospondin-1 (TSP-1), that showed to be of importance for islet angiogenesis and beta-cell function in young mice. The present study aimed to investigate long-term consequences for islet morphology and beta-cell function of TSP-1 deficiency. Islet and beta-cell mass were observed increased at 10–12 weeks of age in TSP-1 deficient mice, but were normalized before 16 weeks of age when compared to wild-type controls. Islet vascularity was normal in 10–12 and 16-week-old TSP-1 deficient animals, whereas islets of one-year-old animals lacking TSP-1 were hypervascular. Beta-cell dysfunction in TSP-1 deficient animals was present at similar magnitudes between 10–12 and 52 weeks of age, as evaluated by glucose tolerance tests. The insulin secretion capacity in vivo of islets in one-year-old TSP-1 deficient animals was only ∼15% of that in wild-type animals. Using a transplantation model, we reconstituted TSP-1 in adult TSP-deficient islets. In contrast to neonatal TSP-1 deficient islets that we previously reported to regain function after TSP-1 reconstitution, adult islets failed to recover. We conclude that TSP-1 deficiency in islets causes changing vascular and endocrine morphological alterations postnatally, but is coupled to a chronic beta-cell dysfunction. The beta-cell dysfunction induced by TSP-1 deficiency is irreversible if not substituted early in life.
Background: The SARS-CoV-2 pandemic has had a significant impact on healthcare delivery. As resources are reallocated, surgery for benign conditions such as gallstone disease is often given low priority. We do not know how this has affected the risk of patients with uncomplicated gallstone disease to develop acute cholecystitis, biliary pancreatitis, or obstructive jaundice. Methods: The study was based on the population-based Swedish Register of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography. The period prior to the first cases of COVID-19 in Sweden, that is, April 2015–March 2020, was compared to the period April 2020–March 2021 during the pandemic. Stratification was made for factors potentially related to priority decisions. Results: Altogether, 78,211 procedures were performed during the period of the study. The ratio of procedures performed during April 2020–March 2021 in the previous 5 years was 0.960 ( p = 0.113). The ratio of procedures on patients aged <65 years was 0.945 ( p = 0.008), on patients aged 65–80 years was 0.964 ( p = 0.423), on patients aged >80 years was 1.336 ( p = 0.025), on men was 1.001 ( p = 0.841), on women was 0.934 ( p = 0.006), on procedures completed laparoscopically was 0.964 ( p = 0.190), on procedures completed with open approach was 0.659 ( p = 0.044), on acute procedures was 1.218 ( p = 0.016), on planned procedures was 0.791 ( p < 0.001), on procedures performed for biliary colic was 0.808 ( p < 0.001), on procedures performed for acute cholecystitis was 1.274 ( p = 0.012), for biliary pancreatitis was 1.192 ( p = 0.037), and for obstructive jaundice was 1.366 ( p = 0.008). Conclusions: The COVID-19 has had a great impact on how gallstone surgery has been organized over the last 2 years. The decreased number of planned procedures probably reflects the reallocation of resources during the pandemic. However, whether the increasing number of acute procedures is the result of postponed planned surgery or a continuation of a long-term trend toward more acute surgery remains unanswered. Further studies are needed to assess and evaluate how this has affected public health and health economics.
The peptide ghrelin is mainly produced in some of the epithelial cells in the stomach, but also, during starvation, by the ε-cells in the endocrine pancreas. Ghrelin, as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R1α), exerts a variety of metabolic functions including stimulation of appetite and weight gain. Its complete role is not yet fully understood, including whether it has any vascular functions. The present study evaluated if ghrelin affects pancreatic and islet blood flow. Ghrelin and the GHS-R1α receptor antagonist GHRP-6 were injected intravenously in rats followed by blood flow measurements using a microsphere technique. Ghrelin decreased, while GHRP-6 in fasted, but not fed, rats selectively increased islet blood flow fourfold. GHS-R1α was identified not only on glucagon-producing cells but also seemed to be present in the islet arterioles. GHRP-6 in fasted rats, only, also improved the peak insulin response to glucose in vivo, thereby substantially blunting the hyperglycemia. GHRP-6 doubled glucose-stimulated insulin release in vitro of both islets obtained from fed and fasted rats. Our results indicate a novel role for endogenous ghrelin acting directly or indirectly as a local vasoconstrictor in the islets during fasting, thereby restricting the insulin response to hyperglycemia. This is to the best of our knowledge the first report that shows this physiological mechanism to restrict insulin delivery from the islets by acting on the vasculature; a mode of action that can be envisaged to complement the previously well-described mechanisms of ghrelin acting directly on the islet endocrine cells.
Irisin is a myokine involved in glucose homeostasis. It is primarily expressed in skeletal muscle, but also in the pancreas. This study aimed to elucidate its presence and role in the islets of Langerhans—i.e., its effect on insulin and glucagon secretion as well as on blood flow in the pancreas. The precursor of irisin, fibronectin type III domain-containing protein 5 (FNDC5), was identified in rat and human islets by both qPCR and immunohistochemistry. Both α- and β-cells stained positive for FNDC5. In human islets, we found that irisin was secreted in a glucose-dependent manner. Neither irisin nor an irisin-neutralizing antibody affected insulin or glucagon secretion from human or rat islets in vitro. The insulin and glucagon content in islets was not altered by irisin. The intravenous infusion of irisin in Sprague Dawley rats resulted in nearly 50% reduction in islet blood flow compared to the control. We conclude that irisin is an islet hormone that has a novel role in pancreatic islet physiology, exerting local vascular effects by diminishing islet blood flow without affecting insulin secretion per se.
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