Karen L. Sweazea

Insulin is an evolutionarily conserved peptide hormone best known for regulating glucose homeostasis, yet its physiological roles extend well beyond glucose regulation. Across the animal kingdom, insulin signaling influences such diverse physiological processes as growth and development, stress responses, cognition, learning, memory formation, sodium balance, thermoregulation, reproduction, and vision. Although traditional laboratory models have advanced our understanding of insulin signaling and diabetes pathophysiology, they represent a relatively narrow perspective on the diversity of glucose regulation strategies and roles of insulin observed in the animal kingdom. Examination of insulin resistance through a comparative physiology lens provides a broader evolutionary framework for understanding how insulin signaling pathways and nutrient regulation have been conserved or modified across species in response to various environmental pressures. Evidence from this approach demonstrates diverse glucose regulation strategies noting that insulin resistance can at times function as an adaptive response to various stressors, even in humans. Several recent reviews have explored the evolution of insulin resistance and adaptive insulin resistance, although most have focused on a limited subset of vertebrates. Therefore, the intent of the present review is not to reproduce these efforts but to synthesize evidence across taxa, highlighting the diversity of strategies for glucose regulation and adaptive insulin resistance in vertebrates through the lens of comparative physiology. By examining insulin signaling within an evolutionary context, this review aims to identify unifying principles that challenge conventional paradigms of insulin resistance as solely pathological and instead position it as a context-dependent physiological adaptation across species.

Being naturally hyperglycemic and insulin insensitive, birds maintain plasma glucose levels twice as high as mammals of similar size. Recent evidence suggests that perturbation of myo-inositol (MI) plays a role in mammalian hyperglycemic regulation. Using an integrative approach, we identify a fundamental role of MI in avian metabolism. We show that MI transporters are highly conserved across birds and that dietary MI reduces fat accumulation in Anna’s hummingbirds. MI consumption by hummingbirds varies with seasonal changes in body mass, consistent with a regulatory role. Furthermore, MI enhances fatty acid oxidation in avian cells, via effects on pyruvate-dehydrogenase complexes, indicating a role in mitochondrial fuel selection. Our findings underscore the importance of MI in avian metabolism, offering insights into their evolutionary adaptations in the context of insulin insensitivity.

Birds have higher plasma glucose concentrations but lower cancer prevalence than other vertebrates. However, this inverse relationship between glucose and cancer may not hold within vertebrate groups. Given that diet affects blood sugar levels, and carnivores have higher cancer risk than herbivores, we also examined whether diet correlates with plasma glucose concentrations. We collected diet, mean plasma glucose concentration, and neoplasia data for up to 273 vertebrate species from existing databases. Across vertebrates, mean plasma glucose concentration negatively correlated with cancer prevalence, but that was mostly driven by differences in mean plasma glucose concentration and cancer prevalence between birds, mammals, and reptiles. Mean plasma glucose concentration was not correlated with diet across vertebrates nor with cancer prevalence within birds, mammals, or reptiles. Primary carnivores had higher neoplasia prevalence than herbivores when controlling for domestication. A hypothetical explanation for our results may be the evolutionary loss or downregulation of genes related to insulin-mediated glucose import in bird cells. This may have led to higher mean plasma glucose concentration, lower intracellular glucose concentrations in the form of glycogen, and production of fewer reactive oxygen species and inflammatory cytokines, potentially contributing to lower neoplasia prevalence in extant birds compared to mammals and reptiles.

Western diets are a public health concern as excess intake of simple sugars and fatty foods, and consequently low consumption of fruits and vegetables, can contribute to obesity and other chronic diseases such as diabetes mellitus, metabolic syndrome, cardiovascular diseases, and cancer. Due to the high prevalence of diseases related to Western diets, the objective of this study was to evaluate whether the inclusion of a novel fiber-rich complex could prevent high fat diet-induced weight gain, adiposity, hyperglycemia, dyslipidemia, and oxidative stress in young male Sprague-Dawley rats, Rattus norvegicus. The novel fiber complex contained a blend of bioactive ingredients: 27% flaxseed, 15.9% wheat bran, 14.8% wheat germ, 10% psyllium, 13.1% brewer’s yeast, and 19.2% grapeseed flour. The study included 24 6-week-old rats divided into three groups that were fed either a control diet (C; standard rodent maintenance diet) containing fiber (3.8%g diet); high-fat diet (H) containing Solka Floc cellulose fiber (6.46%g diet); or high-fat diet in which 5% of the diet was replaced with the novel fiber complex (HF) (total fiber: 5%g fiber complex + 6.14%g Solka Floc). Rats in all diet groups gained significant weight during the 6-week feeding period (p < 0.001) consistent with normal growth. Whereas no differences were observed for blood lipids or beta-hydroxybutyrate, consumption of the H diet significantly increased adiposity (p < 0.001), liver triglycerides (p < 0.001), and fasting whole blood glucose concentrations (p < 0.001) in comparison to the C diet. These effects of high fat consumption were not prevented by the inclusion of the novel fiber complex in this experimental design.

Objective: While fast-food is typically considered highly processed, an analysis to demonstrate this has yet to be conducted. Therefore, the objective of this research was to examine the menu items and ingredients from six fast-food restaurant menus using the NOVA classification. Design: Cross-sectional study. Setting: Data were collected from the top six highest selling US restaurants, per each food category, identified using the Quick Service and Fast Casual Restaurants (QSR) 2020 report. Participants: A total of 740 menu items were identified and classified according to their degree of processing based on ingredient lists using the NOVA classification: minimally processed (MPF), culinary processed ingredient (CPF), processed (PRF) or ultra-processed (UPF). In addition, individual ingredients that appeared on at least three menus were classified into NOVA groups, and the twenty most common ingredients were identified based on frequency of appearance in ingredient lists. Results: Across all menus, 85 % (range: 70–94 %) of items were UPF with only 11 % (range: 6–25 %) being MPF (P < 0·001). Additionally, 46 % of the ingredients that appeared on at least three menus were ultra-processed ingredients. Three ultra-processed ingredients appeared on all six menus: natural flavours, xanthan gum and citric acid. Conclusions: These findings show that the vast majority of menu items from major fast-food restaurants are UPF, and there are few options for MPF. Fast-food companies should consider reformulation or the addition of MPF to the menu to increase healthful food options for their patrons.

Ultra-processed foods (UPF), per the NOVA Classification, provide a major source of calories within modern food systems and are associated with poor health outcomes related to chronic inflammation. Dietary antioxidants play a key role in preventing disease; however, the relationship between the NOVA Classification and the total antioxidant content (TAC) of foods is not well characterised. We hypothesised that TAC would be highest in minimally processed food (MPF), lower in processed food (PRF) and lowest in UPF. TAC data for 3137 animal-based, mixed and plant-based food items were obtained from a published dataset. After data cleaning, 1946 food items and their TAC values were analysed using two hierarchal linear models (alpha: P < 0·05). MPF had the highest mean TAC (10·79 (sem 0·87) mmol/100 g) and were 11·31-fold and 10·72-fold higher than PRF and UPF, respectively (P = 0·023). Plant-based and mixed foods had a higher mean TAC (8·55 (sem 0·68) and 1·12 (sem 0·11) mmol/100 g, respectively) and were 22·67-fold and 2·98-fold higher compared with animal-based foods (P < 0·001). Food processing did not change mean TAC in mixed and animal-based foods; however, plant-based MPF had a higher mean TAC (11·49 (sem 0·93) mmol/100 g) and were 9·88-fold and 15·12-fold higher compared with plant-based PRF and UPF, respectively (P < 0·001). Mean TAC differed between NOVA processing groups for three categories of food: vegetables, beverages and beans, nuts and seeds (P < 0·001). Across all food items, and especially plant-based foods, mean TAC decreased with food processing. The lower TAC of UPF may at least partially explain why their consumption promotes inflammatory chronic disease.