Conceptualization, N.D., A.-S.A.-H.A.-E. and A.A.-R.M.; data curation, S.I.K., A.E.A.-A., L.S.A., M.E.A. and M.H.A.; formal analysis, A.E.A.-A., T.K., N.D., M.M.M.M. and A.-S.A.-H.A.-E.; funding acquisition, M.E.A.; investigation, M.F.D., L.S.A. and A.-S.A.-H.A.-E.; methodology, S.I.K., T.K., N.D., M.M.M.M. and A.A.-R.M.; resources, S.I.K., A.E.A.-A. and L.S.A.; software, A.E.A.-A., T.K., N.D., L.S.A., M.M.M.M., A.-S.A.-H.A.-E., M.E.A., M.H.A. and A.A.-R.M.; supervision, S.I.K. and M.F.D.; validation, M.E.A., M.A. and M.H.A.; visualization, M.F.D.; writing-original draft, T.K., M.M.M.M. and A.A.-R.M.; writing-review and editing, M.H.A., M.A. and A.A.-R.M. All authors have read and agreed to the published version of the manuscript.

Figure 1. Particle sizes analysis with DLS (dynamic light scattering) are presented in the table (A) and the distribution by zeta potential of LPs-CUR is presented in the graph (B).

Figure 1. Particle sizes analysis with DLS (dynamic light scattering) are presented in the table (A) and the distribution by zeta potential of LPs-CUR is presented in the graph (B).

Figure 2. Effect of diabetes (STZ) (65 mg/kg b.wt), 3MA (10 mg/kg b.wt), LPs-CUR (10 mg/kg b.wt.) oral dosing for 10 weeks on (A) serum blood glucose, (B) C-Peptide, (C) Serum insulin, (D) Beta cell function %, (E) insulin resistance. Data expressed as mean ± SE, n = 10 for each group. Each bar carrying the significance which may be significant at * means when p < 0.05, and **** p < 0.0001).

Figure 2. Effect of diabetes (STZ) (65 mg/kg b.wt), 3MA (10 mg/kg b.wt), LPs-CUR (10 mg/kg b.wt.) oral dosing for 10 weeks on (A) serum blood glucose, (B) C-Peptide, (C) Serum insulin, (D) Beta cell function %, (E) insulin resistance. Data expressed as mean ± SE, n = 10 for each group. Each bar carrying the significance which may be significant at * means when p < 0.05, and **** p < 0.0001).

Figure 3. Effect of diabetes (STZ) (65 mg/kg b.wt), 3MA (10 mg/kg b.wt), LPs-CUR (10 mg/kg b.wt.) oral dosing for 10 weeks on (A) MDA., (B) GPX., (C) C.A.T., (D) SOD. in pancreatic tissue of all diabetic and vehicle control groups. Data expressed as mean ± SE, n = 10 for each group. Each bar carrying the significance which may be significant at *** means when p < 0.001 and **** p < 0.0001 at p < 0.001.

Figure 3. Effect of diabetes (STZ) (65 mg/kg b.wt), 3MA (10 mg/kg b.wt), LPs-CUR (10 mg/kg b.wt.) oral dosing for 10 weeks on (A) MDA., (B) GPX., (C) C.A.T., (D) SOD. in pancreatic tissue of all diabetic and vehicle control groups. Data expressed as mean ± SE, n = 10 for each group. Each bar carrying the significance which may be significant at *** means when p < 0.001 and **** p < 0.0001 at p < 0.001.

Figure 4. Effect of diabetes (STZ) (65 mg/kg b.wt), 3MA (10 mg/kg b.wt), LPs-CUR (10 mg/kg b.wt.) oral dosing for ten weeks on serum levels of pro-inflammatory cytokines (A) TNF-α, (B) IFN-Y, (C) IL-6, (D) IL-10 of all diabetic and vehicle control groups. Data expressed as mean ± SE, n = 10 for each group. Each bar carries the significance, which may be significance which may be significant at **** p < 0.0001.

Figure 4. Effect of diabetes (STZ) (65 mg/kg b.wt), 3MA (10 mg/kg b.wt), LPs-CUR (10 mg/kg b.wt.) oral dosing for ten weeks on serum levels of pro-inflammatory cytokines (A) TNF-α, (B) IFN-Y, (C) IL-6, (D) IL-10 of all diabetic and vehicle control groups. Data expressed as mean ± SE, n = 10 for each group. Each bar carries the significance, which may be significance which may be significant at **** p < 0.0001.

Figure 5. Effect of diabetes (STZ) (65 mg/kg b.wt), 3MA (10 mg/kg b.wt), LPs-CUR (10 mg/kg b.wt.) oral dosing for 10 weeks on the expression pattern (Fold change) of genes by qRT-PCR (A) Atf-6, (B) CHOP, (C) JNK., (D) BIP, (E) XBP-1 in pancreatic tissue of all diabetic and vehicle control groups. Data expressed as mean ± SE, n = 10 for each group. Each bar carrying the significance which may be significance which may be significant at ** means when p < 0.01, and **** p < 0.0001).

Figure 5. Effect of diabetes (STZ) (65 mg/kg b.wt), 3MA (10 mg/kg b.wt), LPs-CUR (10 mg/kg b.wt.) oral dosing for 10 weeks on the expression pattern (Fold change) of genes by qRT-PCR (A) Atf-6, (B) CHOP, (C) JNK., (D) BIP, (E) XBP-1 in pancreatic tissue of all diabetic and vehicle control groups. Data expressed as mean ± SE, n = 10 for each group. Each bar carrying the significance which may be significance which may be significant at ** means when p < 0.01, and **** p < 0.0001).

Figure 6. Effect of diabetes (STZ) (65 mg/kg b.wt), 3MA (10 mg/kg b.wt), LPs-CUR (10 mg/kg b.wt.) oral dosing for 10 weeks on the expression pattern (Fold change) of genes by qRT-PCR (A) mic-RNA mir-29b, (B) mir-137, (C) mRNA EIF-2, (D) mRNA P62 (E) mRNA LC3-II, (F) mRNA mTOR, and (G) Beclin-1 in pancreatic tissue of all diabetic and vehicle control groups. Data expressed as mean ± SE, n = 10 for each group. Each bar carrying the significance which may be significance which may be significant at * means when p < 0.05, ** means when p < 0.01, *** means when p < 0.001 and **** p < 0.0001).

Figure 6. Effect of diabetes (STZ) (65 mg/kg b.wt), 3MA (10 mg/kg b.wt), LPs-CUR (10 mg/kg b.wt.) oral dosing for 10 weeks on the expression pattern (Fold change) of genes by qRT-PCR (A) mic-RNA mir-29b, (B) mir-137, (C) mRNA EIF-2, (D) mRNA P62 (E) mRNA LC3-II, (F) mRNA mTOR, and (G) Beclin-1 in pancreatic tissue of all diabetic and vehicle control groups. Data expressed as mean ± SE, n = 10 for each group. Each bar carrying the significance which may be significance which may be significant at * means when p < 0.05, ** means when p < 0.01, *** means when p < 0.001 and **** p < 0.0001).

Figure 7. Representative photomicrograph of the hematoxylin and eosin-stained pancreatic tissue sections showing normal histology of the exocrine and endocrine tissues in the vehicle control rat (A). The STZ-diabetic pancreas shows a diminished islet of the Langerhans size with β cell vacuolations (blue arrowheads), apoptosis (yellow arrowhead), and necrosis (red arrowhead) (B), and periductal mononuclear cell infiltration (blue arrow) with vascular congestion (red arrow) (C). The pancreas of the STZ-3MA-treated animal shows β cell apoptosis (red arrowhead), and necrosis (yellow arrowhead) (D). The pancreas of the STZ-LPs-CUR-treated animal shows vascular congestion (red arrow), periductal mononuclear cell infiltrate (blue arrow), and β cell apoptosis (yellow arrowhead), pyknosis (blue arrowhead), and chromatorhexis (black arrowhead) (E). The pancreas of the STZ-LPs.CUR-3MA-treated animal shows β cell apoptosis (yellow arrowhead), and necrosis (red arrowhead) (F). Scale bars = 30 microns.

Figure 7. Representative photomicrograph of the hematoxylin and eosin-stained pancreatic tissue sections showing normal histology of the exocrine and endocrine tissues in the vehicle control rat (A). The STZ-diabetic pancreas shows a diminished islet of the Langerhans size with β cell vacuolations (blue arrowheads), apoptosis (yellow arrowhead), and necrosis (red arrowhead) (B), and periductal mononuclear cell infiltration (blue arrow) with vascular congestion (red arrow) (C). The pancreas of the STZ-3MA-treated animal shows β cell apoptosis (red arrowhead), and necrosis (yellow arrowhead) (D). The pancreas of the STZ-LPs-CUR-treated animal shows vascular congestion (red arrow), periductal mononuclear cell infiltrate (blue arrow), and β cell apoptosis (yellow arrowhead), pyknosis (blue arrowhead), and chromatorhexis (black arrowhead) (E). The pancreas of the STZ-LPs.CUR-3MA-treated animal shows β cell apoptosis (yellow arrowhead), and necrosis (red arrowhead) (F). Scale bars = 30 microns.

Figure 8. Representative photomicrograph of Beclin-1 stained (A–E) and LC3 stained (F–J) pancreatic tissue sections showing upregulation of both biomarkers’ immunoexpression in the STZ-diabetic animals, notable upregulation of both biomarkers in the STZ-LPs-CUR treated animals, and downregulation of both biomarkers’ immunoexpression in the 3MA, and STZ-LPs.CUR-3MA treated animals.

Figure 8. Representative photomicrograph of Beclin-1 stained (A–E) and LC3 stained (F–J) pancreatic tissue sections showing upregulation of both biomarkers’ immunoexpression in the STZ-diabetic animals, notable upregulation of both biomarkers in the STZ-LPs-CUR treated animals, and downregulation of both biomarkers’ immunoexpression in the 3MA, and STZ-LPs.CUR-3MA treated animals.

Table 1. Primer sequences, accession number, and product size for the quantitative RT-PCR for the analyzed genes in the pancreatic tissue.

Table 1. Primer sequences, accession number, and product size for the quantitative RT-PCR for the analyzed genes in the pancreatic tissue.

GeneForward primer (5′–3′)Reverse Primer (5′–3′)Accession No.Product SizeBclin-1GAATGGAGGGGTCTAAGGCGCTTCCTCCTGGCTCTCTCTNM_001034117.1180LC-3GAAATGGTCACCCCACGAGTACACAGTTTTCCCATGCCCANM_012823.2147MtorGCAATGGGCACGAGTTTGTTAGTGTGTTCACCAGGCCAAANM_019906.294P62GGAAGCTGAAACATGGGCACCCAAGGGTCCACCTGAACAANM_181550.2183EIF-2CTTTCCGGGACAAGATGGCGCTCTGTGAAGTGTGGGGGTCNM_001399818.195ATF6AAGTGAAGAACCATTACTTTATATCTTTCTGCTGGCTATTTGTNM_001107196.1157BIPAACCAAGGATGCTGGCACTAATGACCCGCTGATCAAAGTCNM_013083.2240CHOPCACAAGCACCTCCCAAAGCCTGCTCCTTCTCCTTCATNM_001109986.1158JNKAGTGTAGAGTGGATGCATGAATGTGCTTCCTGTGGTTTACNM_053829.2182XBP1TTACGAGAGAAAACTCATGGGCGGGTCCAACTTGTCCAGAATGCNM_001004210.2289

Table 2. Effect of diabetes (STZ) (65 mg/kg b.wt), 3MA (10 mg/kg b.wt), LPs-CUR (10 mg/kg b.wt.) oral dosing for 10 weeks on the [pancreatic tissue lesion scoring of all treated groups and control.

Table 2. Effect of diabetes (STZ) (65 mg/kg b.wt), 3MA (10 mg/kg b.wt), LPs-CUR (10 mg/kg b.wt.) oral dosing for 10 weeks on the [pancreatic tissue lesion scoring of all treated groups and control.

GroupsAcinar AtrophySize of the Islets of Langerhans in MicrometersBeclin-1 DAB Area FractionLC3 DAB Area FractionControl0.0 b ± 0130.0 a ± 8.4433.52 c ± 1.8633.62 c ± 2.17Diabetic12.0 b ± 2.4975.8 b ± 6.4751.82 b ± 2.9247.36 b ± 1.61Diabetic + 3MA31.0 a ± 6.472.2 b ± 5.9510.61 e ± 1.4212.0 e ± 1.59Diabetic + LPs-CUR1.0 b ± 185.1 b ± 4.2377.13 a ± 0.8272.9 a ± 1.16Diabetic + LPs.CUR-3MA6.0 b ± 2.6780.8 b ± 3.4222.08 d ± 2.2121.18 d ± 2