Cellular and Molecular Imaging of the Diabetic Pancreas
Michel M. J. Modo, Jeff W. M. Bulte in Molecular and Cellular MR Imaging, 2007
Considering the therapeutic implications of being able to measure beta-cell mass in intact subjects and in real time, it becomes important to devise strategies toward overcoming the issues associated with beta-cell imaging. As was mentioned earlier, the endocrine pancreas represents 1 to 2% of the volume of the adult pancreas and is scattered as islets of Langerhans throughout the organ.2 Though beta-cells constitute the majority of the cells in the islets of Langerhans, their proportion might change as the individual ages. Pancreatic islets are organized in a nonrandom fashion and are scattered throughout the acinar tissue of the pancreas.9 Furthermore, in rodents the pancreas is a diffuse organ difficult to isolate in one plane for planar imaging. From a functional perspective, measuring beta-cell mass represents a challenge since BCM is dynamic with compensatory changes (both expansion and involution) to maintain glucose homeostasis. These changes can be in the number or volume of beta-cells in the islet. For example, beta-cell mass is directly proportional to body weight/body mass index.10In the context of diabetes, the dynamic response of the beta-cell to changes in its environment is a major concern, having in mind its exposure to chronic hyperglycemia. With active secretion, granule membrane molecules may be inserted into the plasma membrane to a greater degree, some surface receptors such as GLUT2 and GLP-1 may become downregulated during hyperglycemia, and the cell itself may become degranulated.11
Information on level of drugs into breastmilk
Wendy Jones in Breastfeeding and Medication, 2013
Sulphonylureas Brand names: Gliclazide (Diamicron); Glibenclamide (Daonil, Euglucon); Chlorpropamide; Glimepiride (Amaryl); Glipizide (Glinese, Minodiab), Tolbutamide. US brands: Glibenclamide (Glyburide DiaBeta, Glynase, Micronase); Glimepiride (Amaryl); Glipizide (Glucotrol) Australian brands: Gliclazide (Glyade, Nidem, Diamicron); Glibenclamide (Daonil, Euglucon); Glimepiride (Amaryl); Glipizide (Minodiab, Melizide) Sulphonylureas are oral anti-diabetic agents. They act by augmenting insulin secretion and are useful only where there is residual beta cell activity. All of them can produce hypoglycaemia. They are used in patients who are not overweight or who are unable to tolerate metformin. In women of childbearing age, metformin would be the preferred drug with evidence of reduced morbidity. Theoretically sulphonylureas may produce hypoglycaemia in breastfed infants and it is recommended that they are not used during lactation (BNF). Avoid use during breastfeeding as may produce hypoglycaemia in breastfed infant. Biguanides Biguanides have a different mode of action from sulphonylureas. They decrease gluconeogenesis and increase peripheral utilisation of glucose so there needs to be some residual pancreatic islet cells. It is the drug of choice in overweight patients when lifestyle advice has failed to control symptoms of diabetes. Metformin
Microanatomy and Chemical Coding of Peptide-Containing Neurons in the Digestive Tract
Edwin E. Daniel in Neuropeptide Function in the Gastrointestinal Tract, 2019
The question of whether costored messengers are coreleased has no definite answer. Conceivably, peptides arising from the same precursor are to be found in the same vesicles, although they may show a compartmentalization within the vesicles. This can be exemplified by the glicentin and glucagon immunoreactants in the pancreatic islets.376 Also peptides arising from different precursors are generally found to be colocalized within the same granules. Examples are Met-enkephalin-Arg–Gly–Leu and SP or PHI in enteric neurons,249 CGRP and SP, CGRP and somatostatin, SP and somatostatin in neurons in dorsal root ganglia;377 and glicentin and PYY in gut endocrine cells.378,379 Such colocalized peptides are probably released together. When it comes to coexistence of a neuropeptide and a classical transmitter, the principle seems to be that the neuropeptide is stored in large dense-core vesicles, while the classical transmitter occurs in small “synaptic” vesicles as well. This has been shown by subcellular fractionation for VIP and acetylcholine380 and for NPY and noradrenaline.381 Differential storage indicates that differential release may occur. There is evidence that differential release exists and that it is dependent on the mode and intensity of neuronal stimulation.382–385 Future studies of these mechanisms will hopefully provide us with information on the possible interactions betweeen the various messengers and the possible advantages of multimessenger systems.
A primer on modelling pancreatic islets: from models of coupled β-cells to multicellular islet models
Published in Islets, 2023
Gerardo J. Félix-Martínez, J. Rafael Godínez-Fernández
Pancreatic islets, also known as islets of Langerhans, are mainly composed of ɑ, β and δ-cells, endocrine cells that secrete glucagon, insulin and somatostatin, respectively, critical hormones for the regulation of blood glucose. Insulin, the only hormone capable of reducing glucose levels directly, is secreted when blood glucose rises, producing its hypoglycemic effect by promoting the uptake of glucose by hepatic, muscular and adipose tissues. On the contrary, glucagon is secreted when blood glucose decreases, promoting the release of the stored glucose (i.e., glycogen) mainly from the liver to restore the normal glucose levels. Finally, somatostatin, secreted by δ-cells, is not involved in the regulation of blood glucose directly, although it has a relevant indirect role by inhibiting the secretion of both glucagon and insulin from ɑ and β-cells, respectively.1
Melatonin promotes self-renewal of nestin-positive pancreatic stem cells through activation of the MT2/ERK/SMAD/nestin axis
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Chunyu Bai, Yuhua Gao, Xiangyang Zhang, Wancai Yang, Weijun Guan
In pancreatic islets, a small subset of cells express nestin. These cells, called pancreatic stem cells (PSCs), are thought to be precursors of differentiated pancreatic endocrine cells [13] and play an important role in the growth and maintenance of islets [14–16]. Melatonin can modulate cell function in nestin-positive neural stem cells according to previous research, which prompted us to study whether melatonin can also regulate nestin expression to influence cell fate. In addition, melatonin can combine with melatonin receptor 1 (MT1) on cell membranes to promote the progression of breast cancer by influencing nestin expression in nestin-positive breast cancer stem cells [17]. In our research, we found that nestin-positive PSCs and their differentiated beta cells expressed melatonin receptors 1 (MT1) and 2 (MT2), which are G-protein-coupled receptors. These findings prompted us to study whether melatonin also affects proliferation and differentiation of primary cultured PSCs. In the current study, we measured the viability of primary cultured PSCs in vitro treated with melatonin to verify optimal PSC amplification, demonstrated that melatonin enhanced the self-renewal of the PSCs via the MT2/extracellular signal-regulated kinase (ERK)/SMAD/nestin axis, and suggested a potential molecular mechanism of melatonin that produces these effects.
Reconstructing human pancreatic islet architectures using computational optimization
Published in Islets, 2020
Gerardo J. Félix-Martínez, Aurelio N. Mata, J. Rafael Godínez-Fernández
Pancreatic islets constitute the endocrine part of the pancreas and are essential for glucose homeostasis. It has been estimated that a healthy human pancreas has ∼3 million islets dispersed throughout the pancreas with a mean diameter of 108.9 ± 6.2 μm.1 Pancreatic islets are mainly composed of insulin-producing β-cells (∼65%), glucagon- producing α-cells (∼30%) and somatostatin-producing δ-cells (∼5%),2,3 with other cells such as the ghreling-producing ε-cells4 and the pancreatic polypeptide-producing (PP-) cells5 also present but in a much lower proportion than the α, β and δ-cells.6 Insulin is the only hormone capable of lowering glucose levels directly and glucagon is the main hyperglycemic hormone.7 Somatostatin, on the other hand, inhibits both insulin and glucagon secretion, thus participating indirectly in the regulation of glucose levels.8–10