Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A population of cells containing the enzymes tyrosine hydroxylase (TH) and dopa-decarboxylase (L-AADC) but not dopamine-B-hydroxylase (DBH) nor phenylethanolamine-N-methyltransferase (PNMT) can be detected with immunocytochemical techniques in the pancreas of mouse embryos at the 11th day of development (E 11). The presence of TH in embryonal pancreas is transient: TH is not observed after E 15. By use of a method for simultaneously detecting two antigens in the same section both TH and glucagon were visualized in the same cell on E 12. Double labelled cells comprised 10% of all stained cells. At E 14.5, some of the cells stained for TH also contained insulin. However, at the time somatostatin appeared no embryonal cells containing TH remained. We conclude that two cell types of the APUD series, i.e., the glucagon and insulin cells of pancreas, arise from transformation, in situ, of cells that transiently express a dopaminergic phenotype. These results suggest that peptide-containing cells in skin, brain and gut are linked by a common embryonic origin. They also raise the prospect that other peptidergic cells of the APUD series may have aminergic precursors.
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PMID:Linkage of the brain-skin-gut axis: islet cells originate from dopaminergic precursors. 612 86

Secretory protein-I (SP-I) of parathyroid glands and chromogranin A ( CGA ) of adrenal medullary chromaffin cells are chemically similar if not identical proteins. Both proteins are contained within secretory granules and appear to be cosecreted with granule contents, for example, in the parathyroid with PTH and in the adrenal with epinephrine and dopamine beta-hydroxylase. Antisera to bovine SP-I and porcine CGA , together with antisera to a variety of peptide hormones, were used in an immunofluorescence study of rat tissues in order to determine the probable distribution and cellular localization of these proteins. In addition to their previously demonstrated presence in parathyroid and adrenal cells, the SP-I/ CGA protein family was detected in cells of the thyroid that contained calcitonin and often SRIF but not thyroglobulin; in cells of the anterior pituitary staining for the alpha-subunit of TSH/FSH/LH but not in cells staining for GH, PRL, ACTH, or beta-endorphin; in pancreatic islet cells staining for SRIF and pancreatic polypeptide-related peptides, but not for insulin or glucagon; in the celiac and mesenteric ganglia in cells some of which contained SRIF; and in the gastric antrum in cells containing SRIF, but not gastrin. SP-I/ CGA was not detected in cells of the liver, kidney, parotid gland, or acinar pancreas or in the intermediate or posterior lobes of the pituitary. These results suggest that this protein family enjoys a widespread but highly restricted distribution in many different endocrine-peptide cells of the rat, many that are believed to be of the APUD cell series. The possibility is raised that SP-I/ CGA plays some physiological role in the secretory process or exerts an effect of its own in the periphery after secretion.
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PMID:Selective localization of the parathyroid secretory protein-I/adrenal medulla chromogranin A protein family in a wide variety of endocrine cells of the rat. 623 31

An immunohistochemical and immunoelectron microscopic study was used to demonstrate tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) immunoreactivities in the rat pancreas. Small TH immunoreactive cells were found in close contact with large TH immunonegative ganglion cells among the exocrine glands and were occasionally found in some islets. Some of these TH immunoreactive cells were also DBH immunopositive. The immunoreaction product was seen diffusely in the cytoplasm and in the granule cores of TH immunoreactive cells. All intra-pancreatic ganglion cells were immunoreactive for DBH, but not for TH. The TH immunoreactive cells were identified as small intensely fluorescent (SIF) cells due to their localization and morphological characteristics and showed no insulin, glucagon, somatostatin or pancreatic polypeptide immunoreactivities. These results indicate that SIF cells may release dopamine or noradrenaline to adequate stimuli while the intra-pancreatic ganglion cells with only DBH may not synthesize catecholamines in a normal biosynthetic pathway. TH immunoreactive nerve bundles without varicosities and fibers with varicosities, associated or unassociated with blood vessels, were found in both the exocrine and endocrine pancreas. Close apposition of TH immunoreactive nerve fibers to the smooth muscle and endothelial cells of the blood vessels was observed. A close apposition between TH immunoreactive nerve fibers and exocrine acinar cells and islet endocrine cells was sometimes found in the pancreas. The immunoreaction product was seen diffusely in the axoplasm and in the granular vesicles of the immunoreactive nerve fibers. Since no TH immunoreactive ganglion cells were present in the rat pancreas, the present study suggests that noradrenergic nerve fibers in the pancreas may be extrinsic in origin, and may exert an effect on the regulation of blood flow and on the secretory activity of the acinar cells, duct cells and endocrine cells.
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PMID:Immunocytochemical study of tyrosine hydroxylase and dopamine beta-hydroxylase immunoreactivities in the rat pancreas. 752 36

Norepinephrine (NE) and epinephrine (Epi) help maintain normal blood glucose levels by stimulating glucagon release, glycogenolysis, and food consumption, and by inhibiting insulin release. The absence of NE and Epi in dopamine beta-hydroxylase-null (Dbh-/-) mice results in chronically low blood glucose levels, an impaired glucagon response to hypoglycemia, and elevated insulin levels. Nevertheless, Dbh-/- mice have normal glycogen levels and degrade it normally during a fast. Dbh-/- mice defend blood glucose levels better than controls in an insulin tolerance test but have increased sensitivity to glucose-stimulated insulin secretion and respond normally in a glucose tolerance test. Pharmacological evidence indicates that the hyperinsulinemia results from lack of alpha2-adrenoreceptor stimulation and increased parasympathetic tone. Dbh-/- mice eat normally after challenges with modest levels of insulin or 2-deoxyglucose but fail to eat under more extreme conditions when control mice still do. We suggest that the primary difference in Dbh-/- mice is chronic hyperinsulinemia associated with an altered glucose set point. However, these animals compensate for NE/Epi-mediated glycogenolysis and feeding.
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PMID:Norepinephrine and epinephrine-deficient mice are hyperinsulinemic and have lower blood glucose. 1295 68

Untreated diabetic rats show impaired counterregulation against hypoglycemia. The blunted epinephrine responses are associated with reduced adrenomedullary tyrosine hydroxylase (TH) mRNA levels. Recurrent hypoglycemia further impairs epinephrine counterregulation and is also associated with reduced phenylethanolamine N-methyltransferase mRNA. This study investigated the adaptations underlying impaired counterregulation in insulin-treated diabetic rats, a more clinically relevant model. We studied the effects of insulin treatment on counterregulatory hormones and adrenal catecholamine-synthesizing enzymes and adaptations after recurrent hypoglycemia. Groups included: normal; diabetic, insulin-treated for 3 wk (DI); and insulin-treated diabetic exposed to seven episodes (over 4 d) of hyperinsulinemic-hypoglycemia (DI-hypo) or hyperinsulinemic-hyperglycemia (DI-hyper). DI-hyper rats differentiated the effects of hyperinsulinemia from those of hypoglycemia. On d 5, rats from all groups were assessed for adrenal catecholamine-synthesizing enzyme levels or underwent hypoglycemic clamps to examine counterregulatory responses. Despite insulin treatment, fasting corticosterone levels remained increased, and corticosterone responses to hypoglycemia were impaired in DI rats. However, glucagon, epinephrine, norepinephrine, and ACTH counterregulatory defects were prevented. Recurrent hypoglycemia in DI-hypo rats blunted corticosterone but, surprisingly, not epinephrine responses. Norepinephrine and ACTH responses also were not impaired, whereas glucagon counterregulation was reduced due to repeated hyperinsulinemia. Insulin treatment prevented decreases in basal TH protein and increased PNMT and dopamine beta-hydroxylase protein. DI-hypo rats showed increases in TH, PNMT, and dopamine beta-hydroxylase. We conclude that insulin treatment of diabetic rats protects against most counterregulatory defects but not elevated fasting corticosterone and decreased corticosterone counterregulation. Protection against epinephrine defects, both without and with antecedent hypoglycemia, is associated with enhancement of adrenal catecholamine-synthesizing enzyme levels.
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PMID:Effects of insulin treatment without and with recurrent hypoglycemia on hypoglycemic counterregulation and adrenal catecholamine-synthesizing enzymes in diabetic rats. 1639 86

Caudal brainstem viscerosensory nuclei convey information about the body's internal state to forebrain regions implicated in feeding behavior and responses to immune challenge, and may modulate ingestive behavior following immune activation. Illness-induced appetite loss might be attributed to accentuated "satiety" pathways, activation of a distinct "danger channel" separate from satiety pathways, or both. To evaluate neural substrates that could mediate the effects of illness on ingestive behavior, we analyzed the pattern and phenotypes of medullary neurons responsive to consumption of a preferred food, sweetened milk, and to intraperitoneal lipopolysaccharide challenge that reduced sweetened milk intake. Brainstem sections were stained for c-Fos, dopamine beta-hydroxylase, phenylethanolamine-N-methyltransferase, and glucagon-like peptide-1 (GLP-1) immunoreactivity. Sweetened milk intake activated many neurons throughout the nucleus of the solitary tract (NTS), including A2 noradrenergic neurons in the caudal half of the NTS. LPS challenge activated a similar population of neurons in the NTS, in addition to rostral C2 adrenergic and mid-level A2 noradrenergic neurons in the NTS, many C1 and A1 neurons in the ventrolateral medulla, and in GLP-1 neurons in the dorsal medullary reticular nucleus. Increased numbers of activated GLP-1 neurons in the NTS were only associated with sweetened milk ingestion. Evidence for parallel processing was reflected in the parabrachial nucleus, where sweetened milk intake resulted in activation of the inner external lateral, ventrolateral and central medial portions, whereas LPS challenge induced c-Fos expression in the outer external lateral portions. Thus, signals generated in response to potentially dangerous physiological conditions seem to be propagated via specific populations of catecholaminergic neurons in the NTS and VLM, and likely include a pathway through the external lateral PBN. The data indicate that immune challenge engages multiple ascending neural pathways including both a distinct catecholaminergic "danger" pathway, and a possibly multimodal pathway derived from the NTS.
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PMID:Immune challenge and satiety-related activation of both distinct and overlapping neuronal populations in the brainstem indicate parallel pathways for viscerosensory signaling. 1964 73

Glucagon-like peptide-1 receptor (GLP-1R) agonists, widely used to treat type 2 diabetes, reduce blood pressure (BP) in hypertensive patients. Whether this action involves central mechanisms is unknown. We here report that repeated lateral ventricular (LV) injection of GLP-1R agonist, liraglutide, once daily for 15 days counteracted the development of hypertension in spontaneously hypertensive rats (SHR). In parallel, it suppressed urinary norepinephrine excretion, and induced c-Fos expressions in the area postrema (AP) and nucleus tractus solitarius (NTS) of brainstem including the NTS neurons immunoreactive to dopamine beta-hydroxylase (DBH). Acute administration of liraglutide into fourth ventricle, the area with easy access to the AP and NTS, transiently decreased BP in SHR and this effect was attenuated after lesion of NTS DBH neurons with anti-DBH conjugated to saporin (anti-DBH-SAP). In anti-DBH-SAP injected SHR, the antihypertensive effect of repeated LV injection of liraglutide for 14 days was also attenuated. These findings demonstrate that the central GLP-1R signaling via NTS DBH neurons counteracts the development of hypertension in SHR, accompanied by attenuated sympathetic nerve activity.
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PMID:Central Glucagon-like Peptide-1 Receptor Signaling via Brainstem Catecholamine Neurons Counteracts Hypertension in Spontaneously Hypertensive Rats. 3153 18