Hindbrain A2 noradrenergic neurons assimilate estrogenic and metabolic cues. In female mammals, negative- versus positive-feedback patterns of estradiol (E) secretion impose divergent regulation of the gonadotropin-releasing hormone (GnRH)-pituitary-gonadal (HPG) neuroendocrine axis. Current research used retrograde tracing, dual-label immunocytochemistry, single-cell laser-microdissection, and multiplex qPCR methods to address the premise that E feedback modes uniquely affect metabolic regulation of A2 neurons involved in HPG control. Ovariectomized female rats were given E replacement to replicate plasma hormone levels characteristic of positive (high-E dose) or negative (low-E dose) feedback. Animals were either full-fed (FF) or subjected to short-term, e.g., 18-h food deprivation (FD). After FF or FD, rostral preoptic area (rPO)-projecting A2 neurons were characterized by the presence or absence of nuclear glucokinase regulatory protein (nGKRP) immunostaining. FD augmented or suppressed mRNAs encoding the catecholamine enzyme dopamine-beta-hydroxylase (DβH) and the metabolic-sensory biomarker glucokinase (GCK), relative to FF controls, in nGKRP-immunoreactive (ir)-positive A2 neurons from low-E or high-E animals, respectively. Yet, these transcript profiles were unaffected by FD in nGKRP-ir-negative A2 neurons at either E dosage level. FD altered estrogen receptor (ER)-alpha and ATP-sensitive potassium channel subunit sulfonylurea receptor-1 gene expression in nGKRP-ir-positive neurons from low-E, but not high-E animals. Results provide novel evidence that distinct hindbrain A2 neuron populations exhibit altered versus unaffected transmission to the rPO during FD-associated metabolic imbalance, and that the direction of change in this noradrenergic input is controlled by E feedback mode. These A2 cell types are correspondingly distinguished by FD-sensitive or -insensitive GCK, which correlates with the presence versus absence of nGKRP-ir. Further studies are needed to determine how E signal volume regulates neurotransmitter and metabolic sensor responses to FD in GKRP-expressing A2 neurons.

Diabetic nephropathy (DN) has been recognized as a severe complication of diabetes mellitus and a dominant pathogeny of end-stage kidney disease, which causes serious health problems and great financial burden to human society worldwide. Conventional strategies, such as renin-angiotensin-aldosterone system blockade, blood glucose level control, and bodyweight reduction, may not achieve satisfactory outcomes in many clinical practices for DN management. Notably, due to the multi-target function, Chinese medicine possesses promising clinical benefits as primary or alternative therapies for DN treatment. Increasing studies have emphasized identifying bioactive compounds and molecular mechanisms of reno-protective effects of Chinese medicines. Signaling pathways involved in glucose/lipid metabolism regulation, antioxidation, anti-inflammation, anti-fibrosis, and podocyte protection have been identified as crucial mechanisms of action. Herein, we summarize the clinical efficacies of Chinese medicines and their bioactive components in treating and managing DN after reviewing the results demonstrated in clinical trials, systematic reviews, and meta-analyses, with a thorough discussion on the relative underlying mechanisms and molecular targets reported in animal and cellular experiments. We aim to provide comprehensive insights into the protective effects of Chinese medicines against DN.

UNASSIGNED: Telfairia occidentalis (TO), a plant consumed for its nutritional and medicinal values, exhibits hypoglycaemic effect. However, the metabolic fate of the glucose following TO-induced insulin secretion and consequent hypoglycaemia is not clear.
UNASSIGNED: This study determined the effect of ethyl acetate and n-hexane fractions of TO leaf extracts on some biochemical parameters in the glucose metabolic pathway to explain the possible fate of blood glucose following TO-induced hypoglycaemia.
UNASSIGNED: Eighteen male Wistar rats (180-200 g) divided into control, n-hexane TO fraction- and ethyl acetate TO fraction-treated groups (n = 6/group) were used. The control animals received normal saline while the treated groups received TO at 100 mg/kg for seven days. After 24 h following the last dose, the animals were anaesthetised using ketamine; blood samples were collected and livers harvested to determine some biochemical parameters.
UNASSIGNED: Ethyl acetate TO fraction significantly increased plasma insulin, liver glucokinase activity and plasma pyruvate concentration, but significantly decreased plasma glucose and liver glycogen, without significant changes in plasma lactate, glucose-6-phosphate, liver glucose-6-phosphatase and lactate dehydrogenase activities when compared with control. N-hexane TO fraction significantly reduced liver glucose-6-phosphatase activity and glycogen but significantly increased plasma pyruvate, without significant changes in plasma glucose, insulin, glucose-6-phosphate and lactate concentrations; and liver glucokinase and lactate dehydrogenase activities.
UNASSIGNED: The present study showed that insulin-mediated TO-induced hypoglycaemia resulted in the stimulation of glycolysis and pyruvate production via insulin-dependent and insulin-independent mechanisms.

UNASSIGNED: Telfairia occidentalis (TO) has many biological activities including blood glucose regulation. Thus, it is being used in the treatment of diabetes mellitus. TO has been shown to cause insulin-mediated hypoglycaemia, which leads to post-hypoglycaemic hyperglycaemia. However, the mechanism involved in the post-hypoglycaemic hyperglycaemia is still poorly understood.
UNASSIGNED: This research was designed to determine the response of glucoregulatory hormones and enzymes to TO treatment.
UNASSIGNED: Thirty-five male Wistar rats were divided into seven oral treatment groups (n = 5/group), which received either of 100 mg/kg or 200 mg/kg TO for 7-, 10- or 14 days.
UNASSIGNED: The 7-day treatment with TO significantly increased the levels of insulin, glucagon, and glucose-6-phosphatase (G6Pase) activity but decreased the levels of glucose, adrenaline, and glucokinase (GCK) activity. The 10-day treatment with 100 mg/kg TO increased glucose and decreased GCK activity while 200 mg/kg for the same duration increased glucose, insulin, GCK and G6Pase activities but reduced glucagon. The 14-day treatment with 100 mg/kg TO decreased glucose and glucagon but increased cortisol, while 200 mg/kg TO for same duration increased insulin, but reduced glucagon and GCK activity.
UNASSIGNED: The TO\'s post-hypoglycaemic hyperglycaemia results from increased glucagon and G6Pase activity, and reduced GCK activity. Moreover, the glucagon response mainly depends on glucose rather than insulin.

Islet β-cells are responsible for secreting all circulating insulin in response to rising plasma glucose concentrations. These cells are a phenotypically diverse population that express great functional heterogeneity. In mice, certain β-cells (termed \'hubs\') have been shown to be crucial for dictating the islet response to high glucose, with inhibition of these hub cells abolishing the coordinated Ca2+ oscillations necessary for driving insulin secretion. These β-cell hubs were found to be highly metabolic and susceptible to pro-inflammatory and glucolipotoxic insults. In this study, we explored the importance of hub cells in human by constructing mathematical models of Ca2+ activity in human islets. Our simulations revealed that hubs dictate the coordinated Ca2+ response in both mouse and human islets; silencing a small proportion of hubs abolished whole-islet Ca2+ activity. We also observed that if hubs are assumed to be preferentially gap junction coupled, then the simulations better adhere to the available experimental data. Our simulations of 16 size-matched mouse and human islet architectures revealed that there are species differences in the role of hubs; Ca2+ activity in human islets was more vulnerable to hub inhibition than mouse islets. These simulation results not only substantiate the existence of β-cell hubs, but also suggest that hubs may be favorably coupled in the electrical and metabolic network of the islet, and that targeted destruction of these cells would greatly impair human islet function.